Biology subjects

Su, Z.

Publications and source records attributed to Su, Z..

At least 127 records · Page 7Linked to original sources

bioRxiv2020

Identification of four linear B-cell epitopes on the SARS-CoV-2 spike protein able to elicit neutralizing antibodies

SARS-CoV-2 unprecedentedly threatens the public health at worldwide level. There is an urgent need to develop an effective vaccine within a highly accelerated time. Here, we present the most comprehensive S-protein-based linear B-cell epitope candidate list by combining epitopes predicted by eight widely-used immune-informatics methods with the epitopes curated from literature published between Feb 6, 2020 and July 10, 2020. We find four top prioritized linear B-cell epitopes in the hotspot regions of S protein can specifically bind with serum antibodies from horse, mouse, and monkey inoculated with different SARS-CoV-2 vaccine candidates or a patient recovering from COVID-19. The four linear B-cell epitopes can induce neutralizing antibodies against both pseudo and live SARS-CoV-2 virus in immunized wild-type BALB/c mice. This study suggests that the four linear B-cell epitopes are potentially important candidates for serological assay or vaccine development.

microbiology↗

bioRxiv2020

Endothelial exosome plays functional role during rickettsial infection

Spotted fever group rickettsioses (SFRs) are devastating human infections. Vascular endothelial cells (ECs) are the primary targets of infection. Edema resulting from EC barrier dysfunction occurs in the brain and lungs in most cases of lethal SFR, but the underlying mechanisms remain unclear. The aim of the study is to explore the potential role of Rickettsia (R)-infected, EC-derived exosomes (Exos) during infection. Using size-exclusion chromatography (SEC), we purified Exos from conditioned, filtered, bacteria-free media collected from R-infected human umbilical vein ECs (HUVECs) (R-ECExos) and plasma of R-infected mice (R-plsExos). We observed that rickettsial infection increases the release of heterogeneous plsExos, but endothelial exosomal size, morphology, and production were not significantly altered following infection. Compared to normal plsExos and ECExos, both R-plsExos and R-ECExos induced dysfunction of recipient normal brain microvascular Ecs (BMECs). The effect of R-plsExos on mouse recipient BMEC barrier function is dose-dependent. The effect of R-ECExos on human recipient BMEC barrier function is dependent on exosomal RNA cargo. Next-generation sequencing analysis and stem-loop quantitative reverse transcription PCR (RT-qPCR) validation revealed that R infection triggered the selective enrichment of endothelial exosomal mir-23a and mir-30b, which target the endothelial barrier. To our knowledge, this is the first report on the functional role of extracellular vesicles following infection by obligately intracellular bacteria. ImportanceSpotted fever group rickettsioses are devastating human infections. Vascular endothelial cells are the primary targets of infection. Edema resulting from endothelial barrier dysfunction occurs in the brain and lungs in most cases of lethal rickettsioses, but the underlying mechanisms remain unclear. The aim of the study is to explore the potential role of Rickettsia-infected, endothelial cell-derived exosomes during infection. We observed that rickettsial infection increases the release of heterogeneous plasma Exos, but endothelial exosomal size, morphology, and production were not significantly altered following infection. Rickettsia-infected, endothelial cell-derived exosomes induced dysfunction of recipient normal brain microvascular endothelial cells. The effect is dependent on exosomal RNA cargo. Next-generation sequencing analysis revealed that rickettsial infection triggered the selective enrichment of endothelial exosomal mir-23a and mir-30b, which target the endothelial barrier. To our knowledge, this is the first report on the functional role of extracellular vesicles following infection by obligately intracellular bacteria.

microbiology↗

bioRxiv2020

Mechanistic Dissection of Spatial Organization in NF-κB Signaling Pathways by Hybrid Simulations

The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-{kappa}B) is one of the most important transcription factors involved in the regulation of inflammatory signaling pathways. Inappropriate activation of these pathways has been linked to autoimmunity and cancers. Emerging experimental evidences have been showing the existence of elaborate spatial organizations for various molecular components in the pathways. One example is the scaffold protein tumor necrosis factor receptor associated factor (TRAF). While most TRAF proteins form trimeric quaternary structure through their coiled-coil regions, the N-terminal region of some members in the family can further be dimerized. This dimerization of TRAF trimers can drive them into higher-order clusters as a response to receptor stimulation, which functions as a spatial platform to mediate the downstream poly-ubiquitination. However, the molecular mechanism underlying the TRAF protein clustering and its functional impacts are not well-understood. In this article, we developed a hybrid simulation method to tackle this problem. The assembly of TRAF-based signaling platform at the membrane-proximal region is modeled with spatial resolution, while the dynamics of downstream signaling network, including the negative feedbacks through various signaling inhibitors, is simulated as stochastic chemical reactions. These two algorithms are further synchronized under a multiscale simulation framework. Using this computational model, we illustrated that the formation of TRAF signaling platform can trigger an oscillatory NF-{kappa}B response. We further demonstrated that the temporal patterns of downstream signal oscillations are closely regulated by the spatial factors of TRAF clustering, such as the geometry and energy of dimerization between TRAF trimers. In general, our study sheds light on the basic mechanism of NF-{kappa}B signaling pathway and highlights the functional importance of spatial regulation within the pathway. The simulation framework also showcases its potential of application to other signaling pathways in cells.

systems biology↗

bioRxiv2020

Near-Physiological-Temperature Serial Femtosecond X-ray Crystallography Reveals Novel Conformations of SARS-CoV-2 Main Protease Active Site for Improved Drug Repurposing

The COVID19 pandemic has resulted in 25+ million reported infections and nearly 850.000 deaths. Research to identify effective therapies for COVID19 includes: i) designing a vaccine as future protection; ii) structure-based drug design; and iii) identifying existing drugs to repurpose them as effective and immediate treatments. To assist in drug repurposing and design, we determined two apo structures of Severe Acute Respiratory Syndrome CoronaVirus-2 main protease at ambienttemperature by Serial Femtosecond X-ray crystallography. We employed detailed molecular simulations of selected known main protease inhibitors with the structures and compared binding modes and energies. The combined structural biology and molecular modeling studies not only reveal the dynamics of small molecules targeting main protease but will also provide invaluable opportunities for drug repurposing and structure-based drug design studies against SARS-CoV-2. One Sentence SummaryRadiation-damage-free high-resolution SARS-CoV-2 main protease SFX structures obtained at near-physiological-temperature offer invaluable information for immediate drug-repurposing studies for the treatment of COVID19.

biophysics↗

bioRxiv2020

EPAC regulates von Willebrand factor secretion from endothelial cells in a PI3K/eNOS-dependent manner during inflammation

Coagulopathy is associated with both inflammation and infection, including infection with the novel SARS-CoV-2 (COVID-19). Endothelial cells (ECs) fine tune hemostasis via cAMP-mediated secretion of von Willebrand factor (vWF), which promote the process of clot formation. The exchange protein directly activated by cAMP (EPAC) is a ubiquitously expressed intracellular cAMP receptor that plays a key role in stabilizing ECs and suppressing inflammation. To assess whether EPAC could regulate vWF release during inflammation, we utilized our EPAC1-null mouse model and revealed an increased secretion of vWF in endotoxemic mice in the absence of the EPAC1 gene. Pharmacological inhibition of EPAC1 in vitro mimicked the EPAC1-/- phenotype. EPAC1 regulated TNF-triggered vWF secretion from human umbilical vein endothelial cells (HUVECs) in a phosphoinositide 3-kinases (PI3K)/endothelial nitric oxide synthase (eNOS)-dependent manner. Furthermore, EPAC1 activation reduced inflammation-triggered vWF release, both in vivo and in vitro. Our data delineate a novel regulatory role of EPAC1 in vWF secretion and shed light on potential development of new strategies to controlling thrombosis during inflammation. Key PointPI3K/eNOS pathway-mediated, inflammation-triggered vWF secretion is the target of the pharmacological manipulation of the cAMP-EPAC system.

cell biology↗

bioRxiv2020

Profiles of Expression pattern and tissue distribution of host defense peptides genes in different chicken (Gallus gallus) breeds related to body weight

Host defense peptides (HDPs) are an important first line of defense with antimicrobial and immunomodulatory properties. Selection for increased body weight is suggested to be related to reduced immune response. We studied the relationships among body weight, age, and the HDP expression patterns in intestine and immune organs. We used chickens with marked differences of body sizes. The non-selected Daweishan mini chickens showed the highest indexes of immune organs and the lowest concentrations of the plasma immune parameters C3, C4, IgA, and IgY, while the commercial Avian broiler showed the opposite results. The Daweishan mini chickens showed the highest mRNA expressions of HDP genes in small intestine followed by the semi-selected Wuding chickens. Compared with local breeds, broiler chickens showed higher mRNA expression of HDP genes in spleen, thymus, and bursa. Body weight and HDP expression levels were negatively correlated in the intestine and positively in the immune organs. These results indicated that the HDP immune regulatory roles in small intestine acted as first line of defense in innate immunity in local breeds, and as an adaptive immunity in broiler chickens. Selection was associated with the expression profiles of HDP genes in a chicken, age, and organ-specific manner.

immunology↗

bioRxiv2020

Cadherin clusters stabilized by a combination of specific and nonspecific Cis-Interactions

We demonstrate a combined experimental and computational approach for the quantitative characterization of lateral interactions between membrane-associated proteins. In particular, weak, lateral (cis) interactions between E-cadherin extracellular domains tethered to supported lipid bilayers, were studied using a combination of dynamic single-molecule Forster Resonance Energy Transfer (FRET) and kinetic Monte Carlo (kMC) simulations. Cadherins are intercellular adhesion proteins that assemble into clusters at cell-cell contacts through cis- and trans- (adhesive) interactions. A detailed and quantitative understanding of cis-clustering has been hindered by a lack of experimental approaches capable of detecting and quantifying lateral interactions between proteins on membranes. Here single-molecule intermolecular FRET measurements of wild-type E-cadherin and cis-interaction mutants combined with simulations demonstrate that both nonspecific and specific cis-interactions contribute to lateral clustering on lipid bilayers. Moreover, the intermolecular binding and dissociation rate constants are quantitatively and independently determined, demonstrating an approach that is generalizable for other interacting proteins.

biophysics↗

bioRxiv2020

Transcriptional Profiling Reveals the Transcription Factor Networks Regulating the Survival of Striatal Neurons

The striatum is structurally highly diverse, and its organ functionality critically depends on normal embryonic development. Although several studies have been conducted on the gene functional changes that occur during striatal development, a system-wide analysis of the underlying molecular changes is lacking. Here, we present a comprehensive transcriptome profile that allowed us to explore the trajectory of striatal development and identify the correlation between the striatal development and Huntingtons disease (HD). Furthermore, we applied an integrative transcriptomic profiling approach based on machine learning to systematically map a global landscape of 277 transcription factor (TF) networks. Most of these TF networks are linked to biological processes, and some unannotated genes provide information about the corresponding mechanisms. For example, we found that the Meis2 and Six3 were crucial for the survival of striatal neurons, which was verified using conditional knockout (CKO) mice. Finally, we used RNA-Seq to speculate their downstream targets.

neuroscience↗

bioRxiv2020

A map of cis-regulatory modules and constituent transcription factor binding sites in 77.5% regions of the human genome

Annotating all cis-regulatory modules (CRMs) and transcription factor (TF) binding sites(TFBSs) in genomes remains challenging. We tackled the task by integrating putative TFBSs motifs found in available 6,092 datasets covering 77.47% of the human genome. This approach enabled us to partition the covered genome regions into a CRM candidate (CRMC) set (56.84%) and a non-CRMC set (43.16%). Intriguingly, like known enhancers, the predicted 1,404,973 CRMCs are under strong evolutionary constraints, suggesting that they might be cis-regulator. In contrast, the non-CRMCs are largely selectively neutral, suggesting that they might not be cis-regulatory. Our method substantially outperforms three state-of-the-art methods (GeneHancers, EnhancerAtlas and ENCODE phase 3) for recalling VISTA enhancers and ClinVar variants, as well as by measurements of evolutionary constraints. We estimated that the human genome might encode about 1.46 million CRMs and 67 million TFBSs, comprising about 55% and 22% of the genome, respectively; for both of which, we predicted 80%. Therefore, the cis-regulatory genome appears to be more prevalent than originally thought.

bioinformatics↗

bioRxiv2020

The Coevolution of Promoters and Transcription Factors in Animal and Plant Cells

Coevolution has been acknowledged to play a significant role in driving the evolution of molecules and species. Promoters and transcription factors (TFs), especially their interactions, are key determinants for the regulation of gene expression. However, the evolutionary processes and mechanisms of promoter and TF interactions are still poorly understood. Here we conduct extensive physicochemical analyses of multi-omics sequences in 440 animal species and 223 plant species which span nearly one billion years of phylogeny. We demonstrate that promoters and TFs obey antagonistic coevolution in the animal kingdom while follow mutualistic coevolution in the plant kingdom. Furthermore, we reveal that such two coevolutionary strategies result in different evolutionary transitions of transcriptional networks in the two kingdoms. These results suggest that the two distinct coevolutionary mechanisms are likely to be major drivers of far greater genetic divergence between animals and plants, and open a new door to understanding the roles of promoters and TFs in tumor initiation and progression, and human ageing as well in molecular interactions and evolution.

evolutionary biology↗

bioRxiv2020

Punishment history biases corticothalamic responses to motivationally-significant stimuli

Making predictions about future rewards or punishments is fundamental to adaptive behavior. These processes are influenced by prior experience. For example, prior exposure to aversive stimuli or stressors changes behavioral responses to negative- and positive-value predictive cues. Here, we demonstrate a role for medial prefrontal cortex (mPFC) neurons projecting to the paraventricular nucleus of the thalamus (PVT; mPFC[->]PVT) in this process. We found that a history of punishments negatively biased behavioral responses to motivationally-relevant stimuli in mice and that this negative bias was associated with hyperactivity in mPFC[->]PVT neurons during exposure to those cues. Furthermore, artificially mimicking this hyperactive response with selective optogenetic excitation of the same pathway recapitulated the punishmentinduced negative behavioral bias. Together, our results highlight how information flow within the mPFC[->]PVT circuit is critical for making predictions about imminent motivationally-relevant outcomes as a function of prior experience.

neuroscience↗

bioRxiv2020

Dynamic Changes in Fecal Bacterial Microbiota of Dairy Cattle across the Production Line

Bacteria play important roles in the gastrointestinal tract (GIT) of dairy cattle as the communities are responsible for host health, growth and production performance. However, a systematic characterization and comparison of microbial communities in the GIT of cattle housed in different management units on a modern dairy are still lacking. In this study, we used 16S rRNA sequencing to evaluate the fecal bacterial communities of 90 dairy cattle raised and housed in 12 clearly defined management units on a modern dairy farm. We found that -diversity differed between several pairs of management units, especially between the hutch calves (management unit 1) and the other units except post weaned heifers (management unit 2). Although {beta}-diversity revealed that most of the samples did not cluster according to their management unit membership except management unit 1, in which the samples grouped and separated from others, we observed three major clusters. Besides the hutch calves (management unit 1), most samples from the other 11 units formed two distinct clusters and the relative abundance of Patescibacteria might be the reason for the separation. Moreover, we identified 212 amplicon sequence variants (ASVs) with relative abundances > 0.1% in more than 10% of the total samples that had significantly different abundances in these units. Furthermore, we found that, as the calves aged, 19 ASVs that were exclusively detected in unit 1, gradually degraded and never reoccurred in other management units. Lastly, we recognized 181 pairs of interactions between 61 ASVs with possibly strong synergistic or antagonistic relationships. These results suggest the enteric microbial communities of dairy cattle housed in different management units are quite dynamic. IMPORTANCEBacterial communities of GIT are crucial for ruminants, such as dairy cattle since they contribute to not only the cattles physiology and health but also milk production and food safety that are closely related to human health. Both scientifically and agriculturally, it is necessary to have deep insights into the composition and changes of the bacteria on modern dairy farms. In this study, we provided the profiles of fecal bacterial communities of dairy cattle in each management unit on a modern dairy and described how the enteric microbial communities changed across these management units. The findings have implications for improving animal health, dairy production, farm management, and food safety.

microbiology↗

bioRxiv2020

A Multiscale and Comparative Model for Receptor Binding of 2019 Novel Coronavirus and the Implication of its Life Cycle in Host Cells

The respiratory syndrome caused by a new type of coronavirus has been emerging from China and caused more than one million death globally since December 2019. This new virus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the same receptor called Angiotensin-converting enzyme 2 (ACE2) to attack humans as the coronavirus that caused the severe acute respiratory syndrome (SARS) seventeen years ago. Both viruses recognize ACE2 through the spike proteins (S-protein) on their surfaces. It was found that the S-protein from the SARS coronavirus (SARS-CoV) bind stronger to ACE2 than SARS-CoV-2. However, function of a bio-system is often under kinetic, rather than thermodynamic, control. To address this issue, we constructed a structural model for complex formed between ACE2 and the S-protein from SARS-CoV-2, so that the rate of their association can be estimated and compared with the binding of S-protein from SARS-CoV by a multiscale simulation method. Our simulation results suggest that the association of new virus to the receptor is slower than SARS, which is consistent with the experimental data obtained very recently. We further integrated this difference of association rate between virus and receptor into a mathematical model which describes the life cycle of virus in host cells and its interplay with the innate immune system. Interestingly, we found that the slower association between virus and receptor can result in longer incubation period, while still maintaining a relatively higher level of viral concentration in human body. Our computational study therefore provides, from the molecular level, one possible explanation that this new pandemic by far spread much faster than SARS.

biophysics↗

bioRxiv2020

Hydrogen evolution and absorption phenomena in plasma membrane of higher plants

Molecular hydrogen (H2) exhibits a wide breadth of botanical effects especially in improving the resistance to abiotic stress. However, the primary target is not clear. Bidirectional hydrogenases have been well studied in microbes and alga, but there is a paucity of research in higher plants. Here, we used real-time spectrophotometry, gas chromatography and H2 sensor to detect the H2-evolving and H2-uptake activity of the plasma membrane (PM) vesicles of higher plants. Net H+, Na+ and K+ fluxes were measured using Non-invasive Micro-test Technology (NMT). We found that the PM vesicles of Vigna radiata hypocotyls and Capsicum annuum stems have the ability of both oxidizing and producing H2. This two-way enzymatic activity coupled with the redox of ferricyanide/ferrocyanide and NADH/NAD+. H2 affected the H+ and Na+ fluxes on the surface of V. radiata hypocotyls. These results demonstrate that the PM vesicles of higher plants have the abilities of H2 evolution and absorption. The bidirectional activities may act as a valve to regulate the energy balance in plant cells.

biochemistry↗

bioRxiv2019

tRNA-derived fragments and microRNAs in the maternal-fetal interface of a mouse maternal-immune-activation autism model

tRNA-derived small fragments (tRFs) and tRNA halves have emerging functions in different biological pathways, such as regulating gene expression, protein translation, retrotransposon activity, transgenerational epigenetic changes and response to environmental stress. However, small RNAs like tRFs and microRNAs in the maternal-fetal interface during gestation have not been studied extensively. Here we investigated the small RNA composition of mouse placenta/decidua, which represents the interface where the mother communicates with the fetus, to determine whether there are specific differences in tRFs and microRNAs during fetal development and in response to maternal immune activation (MIA). Global tRF expression pattern, just like microRNAs, can distinguish tissue types among placenta/decidua, fetal brain and fetal liver. In particular, 5 tRNA halves from tRNAGly, tRNAGlu, tRNAVal and tRNALys are abundantly expressed in the normal mouse placenta/decidua. Moreover, tRF and microRNA levels in the maternal-fetal-interface change dynamically over the course of embryonic development. To see if stress alters non-coding RNA expression at the maternal-fetal interface, we treated pregnant mice with a viral infection mimetic, which has been shown to promote autism-related phenotypes in the offspring. Acute changes in the levels of specific tRFs and microRNAs were observed 3-6 hours after MIA and are suppressed thereafter. A group of 5 tRNA halves is down-regulated by MIA, whereas a group of 18-nucleotide tRF-3a is up-regulated. In conclusion, tRFs show tissue-specificity, developmental changes and acute response to environmental stress, opening the possibility of them having a role in the fetal response to MIA.

molecular biology↗

bioRxiv2019

Annexin A2 depletion exacerbates the intracerebral microhemorrhage induced by acute rickettsia and Ebola virus infections

Intracerebral microhemorrhages (CMHs) are small foci of hemorrhages in the cerebrum. Acute infections induced by some intracellular pathogens, including rickettsia, can result in CMHs. Annexin a2 (ANXA2) has been documented to play a functional role during intracellular bacterial adhesion. Here we report that ANXA2-knockout (KO) mice are more susceptible to CMHs in response to rickettsia and Ebola virus infections, suggesting an essential role of ANXA2 in protecting vascular integrity during these intracellular pathogen infections. Proteomic analysis via mass spectrometry of whole brain lysates and brain-derived endosomes from ANXA2-KO and wild-type (WT) mice post-infection with R. australis revealed that a variety of significant proteins were differentially expressed, and the follow-up function enrichment analysis had identified several relevant cell-cell junction functions. Immunohistology study confirmed that both infected WT and infected ANXA2-KO mice were subjected to adherens junctional protein (VE-cadherin) damages. However, key blood-brain barrier (BBB) components, tight junctional proteins ZO-1 and occludin, were disorganized in the brains from R. australis-infected ANXA2-KO mice, but not those of infected WT mice. Similar ANXA2-KO dependent CMHs and fragments of ZO-1 and occludin were also observed in Ebola virus-infected ANXA2-KO mice, but not found in infected WT mice. Overall, our study revealed a novel role of ANXA2 in the formation of CMHs during R. australis and Ebola virus infections; and the underlying mechanism is relevant to the role of ANXA2-regulated tight junctions and its role in stabilizing the BBB in these deadly infections. Author SummaryTraditionally, spontaneous intracerebral microhemorrhages (CMHs) were defined as small foci of intracerebral hemorrhages. Such atraumatic CMHs are due to the rupture of a weak blood vessel wall. Infections complicating cerebrovascular accidents have been extensively investigated. However, the role of CMHs complicating infections, in particularly acute systemic infections, has been poorly explored. Population-based retrospective cohort studies suggest there are potentially more undiscovered cases of CMHs accompanying acute systemic infections. Given both the lack of an animal model and cellular/molecular pathophysiology of CMHs following acute systemic infections, there is an urgent need to increase our comprehensive understanding of acute infection-induced CMHs. Overall, our study revealed a novel role of annexin a2 (ANXA2) in the formation of CMHs during R. australis and Ebola virus infections; and the underlying mechanism is relevant to the role of ANXA2-regulated endothelial tight junctions and its role in stabilizing the blood-brain barrier in these deadly infections.

pathology↗

bioRxiv2019

ATAC-seq identifies thousands of extrachromosomal circular DNA in cancers and cell lines

Extrachromosomal circular DNAs (eccDNAs) lack centromeres and are not passed equally into daughter cells and thus provide a source of cell-cell heterogeneity in normal and tumor cells. Previously we and other groups purified circular DNA and linearized them by rolling circle amplification for paired end high throughput sequencing to identify eccDNA in cells and tissues. We hypothesized that many eccDNA will have more open chromatin and so will be susceptible to linearization and sequencing by tagmentation. Indeed, we find that ATAC-seq on cell lines and cancers, without any enrichment of circular DNA, identifies thousands of eccDNAs. The identified eccDNAs in cell lines were validated by inverse PCR on DNA that survives exonuclease digestion of linear DNA and by metaphase FISH. We demonstrate that ATAC-seq data generated in Lower Grade Gliomas (LGG) and Glioblastomas (GBM) identify eccDNAs, including one containing the well-known EGFR gene amplicon from chr7. Many of the eccDNAs are identified even before amplification of the locus is detected by genotyping arrays. Thus, standard ATAC-seq is a sensitive method to detect segments of DNA that are present as eccDNA in a subset of the tumor cells, ready to be further amplified under appropriate selection, as during therapy.

genomics↗

bioRxiv2019

miR-206 family is important for mitochondrial and muscle function, but not essential for myogenesis in vitro

miR-206, miR-1a-1 and miR-1a-2 are induced during differentiation of skeletal myoblasts and promote myogenesis in vitro. miR-206 is required for skeletal muscle regeneration in vivo. Although this microRNA family is hypothesized to play an essential role in differentiation, a triple knockout of the three genes has not been done to test this hypothesis. We report that triple KO C2C12 myoblasts generated using CRISPR/Cas9 method differentiate despite the expected de-repression of the microRNA targets. Surprisingly, their mitochondrial function is diminished. Triple KO mice demonstrate partial embryonic lethality, most likely due to the role of miR-1a in cardiac muscle differentiation. Two triple KO mice survive and grow normally to adulthood with smaller myofiber diameter and diminished physical performance. Thus, unlike other microRNAs important in other differentiation pathways, the miR-206 family is not absolutely essential for myogenesis and is instead a modulator of optimal differentiation of skeletal myoblasts.

molecular biology↗