Biology subjects

Sun, Q.

Publications and source records attributed to Sun, Q..

At least 127 records · Page 7Linked to original sources

bioRxiv2023

Establishment and Evaluation of Rat Models of Cervical Spondylopathy with Yin Deficiency Syndrome

ObjectiveCervical spondylosis (CS) with Yin deficiency syndrome is an important classification of traditional Chinese medicine (TCM) symptoms of CS. However, there is no animal model for studying this TCM syndrome. This study aimes to establish and evaluate rat models of cervical spondylopathy with Yin deficiency syndrome. MethodThirty-six Sprague-Dawley male rats were randomly divided into the blank control (control), CS and CS with Yin deficiency syndrome (YCS) groups (n = 12 rats/group). CS was induced using cervical static-dynamic imbalance to mimic disk degeneration (except in the control group). After 30 days of the CS rat model, rats in the YCS group were subjected to sustained sleep deprivation for 168h. After different induction times, the rats in each group were observed for behavior and weight. Pain behavior was assessed by a withdrawal response to von Frey filament application, and heart rate and blood pressure were measured using a rat noninvasive sphygmomanometer. Intervertebral disc pathology sections were observed using hematoxylin and eosin staining and an electron microscope. Western blotting was used to evaluate the protein level of collagen-II, Bcl-2, Bax and Bcl-2/Bax expression in the cervical intervertebral disc. Determination of related laboratory serum indexes, cyclic adenosine monophosphate, and cyclic guanosine phosphate were conducted using enzyme-linked immunosorbent assay. ResultsThe laboratory indexes in the YCS group were significantly different from those in the control and CS groups (P < 0.05), and indicators of 72-, 120-, and 178-h sleep deprivation showed varying degrees of difference from those of the CS group. ConclusionAfter establishing a model of CS, continuous sleep deprivation for 72 h was used to create a rat model of CS with Yin deficiency syndrome. The established rat models of CS with Yin deficiency syndrome met the clinical and Chinese medicine characteristics, and thus, they can be expected to become an ideal model for studying CS with Yin deficiency syndrome in the future.

zoology↗

bioRxiv2023

Sox11 is enriched in myogenic progenitors but dispensable for development and regeneration of skeletal muscle.

Transcription factors (TFs) play key roles in regulating the differentiation and function of stem cells, including muscle satellite cells (MuSCs), a resident stem cell population responsible for postnatal regeneration of the skeletal muscle. Sox11 belongs to the Sry-related HMG-box (SOX) family of TFs that play diverse roles in stem cell behavior and tissue specification. Analysis of single-cell RNA-sequencing (scRNA-seq) datasets identify a specific enrichment of Sox11 mRNA in differentiating but not quiescent MuSCs. Consistent with the scRNA-seq data, Sox11 levels increase during differentiation of murine primary myoblasts in vitro. scRNA-seq data comparing muscle regeneration in young and old mice further demonstrate that Sox11 expression is reduced in aged MuSCs. Age-related decline of Sox11 expression is associated with reduced chromatin contacts within the topologically associated domains. Unexpectedly, Myod1Cre-driven deletion of Sox11 in embryonic myoblasts has no effects on muscle development and growth, resulting in apparently healthy muscles that regenerate normally. Pax7CreER or Rosa26CreER driven (MuSC-specific or global) deletion of Sox11 in adult mice similarly has no effects on MuSC differentiation or muscle regeneration. These results identify Sox11 as a novel myogenic differentiation marker with reduced expression in quiescent and aged MuSCs, but the specific function of Sox11 in myogenesis remain to be elucidated.

cell biology↗

bioRxiv2023

Coupling of Slack and NaV1.6 sensitizes Slack to quinidine blockade and guides anti-seizure strategy development

Quinidine has been used as an anticonvulsant to treat patients with KCNT1-related epilepsy by targeting gain-of-function KCNT1 pathogenic mutant variants. However, the detailed mechanism underlying quinidines blockade against KCNT1 (Slack) remains elusive. Here, we report a functional and physical coupling of the voltage-gated sodium channel NaV1.6 and Slack. NaV1.6 binds to and highly sensitizes Slack to quinidine blockade. Homozygous knockout of NaV1.6 reduces the sensitivity of native sodium-activated potassium currents to quinidine blockade. NaV1.6-mediated sensitization requires the involvement of NaV1.6s N-and C-termini binding to Slacks C-terminus, and is enhanced by transient sodium influx through NaV1.6. Moreover, disrupting the Slack-NaV1.6 interaction by viral expression of Slacks C-terminus can protect against SlackG269S-induced seizures in mice. These insights about a Slack-NaV1.6 complex challenge the traditional view of "Slack as an isolated target" for anti-epileptic drug discovery efforts, and can guide the development of innovative therapeutic strategies for KCNT1-related epilepsy. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=134 SRC="FIGDIR/small/532982v3_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1127858org.highwire.dtl.DTLVardef@19ad9f4org.highwire.dtl.DTLVardef@15b5542org.highwire.dtl.DTLVardef@13a86b4_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Title: Leveraging Base Pair Mammalian Constraint to Understand Genetic Variation and Human Disease

Although thousands of genomic regions have been associated with heritable human diseases, attempts to elucidate biological mechanisms are impeded by a general inability to discern which genomic positions are functionally important. Evolutionary constraint is a powerful predictor of function that is agnostic to cell type or disease mechanism. Here, single base phyloP scores from the whole genome alignment of 240 placental mammals identified 3.5% of the human genome as significantly constrained, and likely functional. We compared these scores to large-scale genome annotation, genome-wide association studies (GWAS), copy number variation, clinical genetics findings, and cancer data sets. Evolutionarily constrained positions are enriched for variants explaining common disease heritability (more than any other functional annotation). Our results improve variant annotation but also highlight that the regulatory landscape of the human genome still needs to be further explored and linked to disease.

genomics↗

bioRxiv2023

SAKit: an all-in-one analysis pipeline for identifying novel protein caused by variant events at genomic and transcriptic level

SummaryGenetic modifications that cause pivotal protein inactivation or abnormal activation may lead to cell signaling pathway change or even dysfunction, resulting in cancer and other diseases. In turn, dysfunction will further produce "novel proteins" that do not exist in the canonical human proteome. Identification of novel proteins is meaningful for identifying promising drug targets and developing new therapies. In recent years, several tools have been developed for identifying DNA or RNA variants with the extensive application of nucleotide sequencing technology. However, these tools mainly focus on point mutation and have limited performance in identifying large-scale variants as well as the integration of mutations. Here we developed a hybrid Sequencing Analysis bioinformatic pipeline by integrating all relevant detection Kits(SAKit): this pipeline fully integrates all variants at the genomic and transcriptomic level that may lead to the production of novel proteins defined as proteins with novel sequences compare to all reference sequences by comprehensively analyzing the long and short reads. The analysis results of SAKit demonstrate that large-scale mutations have more contribution to the production of novel proteins than point mutations, and long-read sequencing has more advantages in large-scale mutation detection. Availability and implementationSAKit is freely available on docker image (https://hub.docker.com/repository/docker/therarna/sakit), which is mainly implemented within a Snakemake framework in Python language.

bioinformatics↗

bioRxiv2023

Mass-immigration shapes the antibiotic resistome of wastewater treatment plants

Wastewater treatment plants (WWTPs) are the hotspots for the spread of antibiotic resistance genes (ARGs) into the environment. Nevertheless, a comprehensive assessment of the city-level and short-term daily variations of ARG surveillance is still lacking in WWTPs. Here, 285 ARGs and ten mobile gene elements (MGEs) were monitored in seven WWTPs in Xiamen via high-throughput qPCR (HT-qPCR) for seven days. The average daily load of ARGs to WWTPs was about 1.21 x 1020 copies/d, and a total of 1.44 x 1018 copies/d was discharged to the environment across the entire city. Interestingly, no daily variations were observed in ARG richness, abundance, and community composition. Stochastic processes were the main force determining the assembly of ARG communities, with their relative importance ranked in the order of influent (INF) > effluent (EFF) > activated sludge (AS). Further analyses indicated that bacteria and ARGs from upstream treatment units played an increasingly dominant role in shaping ARG communities in AS and EFF, respectively, suggesting the importance of mass-immigration of bacteria and ARGs from the source on ARG transport in wastewater treatment units. This emphasizes the need to revise the way we mitigate ARG contamination but focus on the source of ARGs in urban wastewater.

microbiology↗

bioRxiv2023

Whole-genome sequencing of ethnolinguistic diverse northwestern Chinese Hexi Corridor people from the 10K_CPGDP project suggested the differentiated East-West genetic admixture along the Silk Road and their biological adaptations

The ancient Silk Road served as the main connection between East and West Eurasia for several centuries. At any rate, the genetic exchange between populations along the ancient Silk Road was likely to leave traces on the contemporary gene pool of local people in Northwest China, which was the passage of the Northern Silk Road. However, genetic sources from northwestern China are under-represented in the current population-scale genomic database. To characterize the genetic architecture and adaptative history of the Northern Silk Road ethnic populations, we performed whole-genome sequencing on 126 individuals from six ethnolinguistic groups (Tibeto-Burman (TB)-speaking Tibetan, Mongolic (MG)-speaking Dongxiang/Tu/eastern Yugur, and Turkic (TK)-speaking Salar/western Yugur) living in Gansu and Qinghai in the 10K Chinese people Genomic Diversity Project (10K_CPGDP). We observed ethnicity-related differentiated population structures among these geographically close Northwest Chinese populations, that is, Salar and Tu people showed a close affinity with southwestern TB groups, and other studied populations shared more alleles with MG and Tungusic groups. Overall, the patterns of genetic clustering were not consistent with linguistic classifications. We estimated that Dongxiang, Tibetan, and Yugur people inherited more than 10% West Eurasian ancestry, much higher than that of Salar and Tu people (<7%). Hence, the difference in the proportion of West Eurasian ancestry has primarily contributed to the genetic divergence of geographically close Northwest Chinese populations. The signatures of natural selection were identified in genes associated with cardiovascular system diseases or lipid metabolism related to triglyceride levels (e.g., PRIM2, PDE4DIP, NOTCH2, DDAH1, GALNT2, and MLIP) and developmental and neurogenetic diseases (e.g., NBPFs 8/9/20/25P, etc.). Moreover, the EPAS1 gene, a transcription factor regulating hypoxia response, showed relatively high PBS values in our studied groups. The sex-biased admixture history, in which the West Eurasian ancestry was introduced primarily by males, was identified in Dongxiang, Tibetan, and Yugur populations. We determined that the eastern-western admixture occurred [~]783-1131 years ago, coinciding with the intensive economic and cultural exchanges during the historic Trans-Eurasian cultural exchange era.

genomics↗

bioRxiv2023

Integrating lipid metabolism, pheromone production and perception by Fruitless and Hepatocyte nuclear factor 4

Sexual attraction and perception, governed by separate genetic circuits in different organs, are crucial for mating and reproductive success, yet the mechanisms of how these two aspects are integrated remain unclear. In Drosophila, the male-specific isoform of Fruitless (Fru), FruM, is known as a master neuro-regulator of innate courtship behavior to control perception of sex pheromones in sensory neurons. Here we show that the non-sex specific Fru isoform (FruCOM) is necessary for pheromone biosynthesis in hepatocyte-like oenocytes for sexual attraction. Loss of FruCOM in oenocytes resulted in adults with reduced levels of the cuticular hydrocarbons (CHCs), including sex pheromones, and show altered sexual attraction and reduced cuticular hydrophobicity. We further identify Hepatocyte nuclear factor 4 (Hnf4) as a key target of FruCOM in directing fatty acid conversion to hydrocarbons in adult oenocytes. fru- and Hnf4-depletion disrupts lipid homeostasis, resulting in a novel sex-dimorphic CHC profile, which differs from doublesex- and transformer-dependent sexual dimorphism of the CHC profile. Thus, Fru couples pheromone perception and production in separate organs for precise coordination of chemosensory communication that ensures efficient mating behavior. TeaserFruitless and lipid metabolism regulator HNF4 integrate pheromone biosynthesis and perception to ensure robust courtship behavior.

developmental biology↗

bioRxiv2023

Area postrema neurons mediate interleukin-6 function in cancer-associated cachexia

Interleukin-6 (IL-6) has been long considered a key player in cancer-associated cachexia1-15. It is believed that sustained elevation of IL-6 production during cancer progression causes brain dysfunctions, which ultimately result in cachexia16-20. However, how peripheral IL-6 influences the brain remains poorly understood. Here we show that neurons in the area postrema (AP), a circumventricular structure in the hindbrain, mediate the function of IL-6 in cancer-associated cachexia in mice. We found that circulating IL-6 can rapidly enter the AP and activate AP neurons. Peripheral tumor, known to increase circulating IL-61-5,15,18,21-23, leads to elevated IL-6 and neuronal hyperactivity in the AP, and causes potentiated excitatory synaptic transmission onto AP neurons. Remarkably, neutralization of IL-6 in the brain of tumor-bearing mice with an IL-6 antibody prevents cachexia, reduces the hyperactivity in an AP network, and markedly prolongs lifespan. Furthermore, suppression of Il6ra, the gene encoding IL-6 receptor, specifically in AP neurons with CRISPR/dCas9 interference achieves similar effects. Silencing of Gfral-expressing AP neurons also ameliorates the cancer-associated cachectic phenotypes and AP network hyperactivity. Our study identifies a central mechanism underlying the function of peripheral IL-6, which may serve as a target for treating cancer-associated cachexia.

neuroscience↗

bioRxiv2022

Multiple founding paternal lineages inferred from the newly-developed SNPSeqTyper 639 Y-SNP panel suggested the complex admixture and migration history of Chinese people

Non-recombining regions of the Y-chromosome are inherited male-specifically and recorded the evolutionary traces of male human populations. Recent whole Y-chromosome sequencing studies have identified previously unrecognized population divergence, expansion and admixture processes, which promotes a better understanding and application of the observed patterns of Y-chromosome genetic diversity. Here, we developed one highest-resolution Y-SNP panel for forensic pedigree search and paternal biogeographical ancestry inference, which included 639 phylogenetically informative SNPs (Y-SNPs). We genotyped these loci in 1033 Chinese male individuals from 33 ethnolinguistically diverse populations and identified 257 terminal Y-chromosomal lineages with frequency ranging from 0.010 (singleton) to 0.0687. We identified six dominant common founding lineages associated with different ethnolinguistic backgrounds, which included O2a2b1a1a1a1a1a1a1-M6539, O2a1b1a1a1a1a1a1-F17, O2a2b1a1a1a1a1b1a1b-MF15397, O2a2b2a1b1-A16609, O1b1a1a1a1b2a1a1-F2517 and O2a2b1a1a1a1a1a1-F155. The AMOVA and nucleotide diversity estimates revealed considerable differences and high genetic diversity among ethnolinguistically different populations. We constructed one representative phylogenetic tree among 33 studied populations based on the haplogroup frequency spectrum and sequence variations. Clustering patterns in principal component analysis and multidimensional scaling results showed a genetic differentiation between Tai-Kadai-speaking Li, Mongolic-speaking Mongolian and other Sinitic-speaking Han Chinese populations. Phylogenetic topology inferred from the BEAST and Network relationships reconstructed from the popART further showed the founding lineages from culturally/linguistically diverse populations, such as C2a/C2b was dominant in Mongolian people and O1a/O1b was dominant in island Li people. We also identified many lineages shared by more than two ethnolinguistically different populations with a high proportion, suggesting their extensive admixture and migration history. Our findings indicated that our developed high-resolution Y-SNP panel included major dominant Y-lineages of Chinese populations from different ethnic groups and geographical regions, which can be used as the primary and powerful tool for forensic practice. We should emphasize the necessity and importance of whole-sequencing of more ethnolinguistically different populations, which can help identify more unrecognized population-specific variations for the final promotion of Y-chromosome-based forensic applications.

genetics↗

bioRxiv2022

DeepGWAS: Enhance GWAS Signals for Neuropsychiatric Disorders via Deep Neural Network

Genetic dissection of neuropsychiatric disorders can potentially reveal novel therapeutic targets. While genome-wide association studies (GWAS) have tremendously advanced our understanding, we approach a sample size bottleneck (i.e., the number of cases needed to identify >90% of all loci is impractical). Therefore, computationally enhancing GWAS on existing samples may be particularly valuable. Here, we describe DeepGWAS, a deep neural network-based method to enhance GWAS by integrating GWAS results with linkage disequilibrium and brain-related functional annotations. DeepGWAS enhanced schizophrenia (SCZ) loci by [~]3X when applied to the largest European GWAS, and 21.3% enhanced loci were validated by the latest multi-ancestry GWAS. Importantly, DeepGWAS models can be transferred to other neuropsychiatric disorders. Transferring SCZ-trained models to Alzheimers disease and major depressive disorder, we observed 1.3-17.6X detected loci compared to standard GWAS, among which 27-40% were validated by other GWAS studies. We anticipate DeepGWAS to be a powerful tool in GWAS studies.

genetics↗

bioRxiv2022

Mechanisms of HIV-1 Integrase Resistance to Dolutegravir and Potent Inhibition of Drug Resistant Variants

HIV-1 infection depends on the integration of viral DNA into host chromatin. Integration is mediated by the viral enzyme integrase and is blocked by integrase strand transfer inhibitors (INSTIs), first-line antiretroviral therapeutics widely used in the clinic. Resistance to even the best INSTIs is a problem and the mechanisms of resistance are poorly understood. Here, we analyze combinations of the mutations E138K, G140A/S, and Q148H/K/R, which confer resistance to INSTIs. The investigational drug 4d more effectively inhibited the mutants compared with the approved drug Dolutegravir (DTG). We present 11 new cryo-EM structures of drug resistant HIV-1 intasomes bound to DTG or 4d, with better than 3 [A] resolution. These structures, complemented with free energy simulations, virology, and enzymology, explain the mechanisms of DTG resistance involving E138K+G140A/S+Q148H/K/R and show why 4d maintains potency better than DTG. These data establish a foundation for further development of INSTIs that potently inhibit resistant forms in integrase.

biophysics↗

bioRxiv2022

Recognition of Galactose by a Scaffold Protein Recruits a Transcriptional Activator for the GAL Regulon Induction in Candida albicans

The GAL pathway of yeasts has long served as a model system for understanding of how regulatory mode of eukaryotic metabolic pathways evolves. While Gal4 mode has been well-characterized in Saccharomycetaceae clade, little is known about the regulation of the GAL pathway in other yeasts. Here, we find that Rep1, a Ndt80-like family transcription factor, serves as a galactose sensor in the commensal-pathogenic fungus Candida albicans. It is presented at the GAL gene promoters independent of the presence of galactose. Rep1 recognizes galactose via a direct physical interaction. The net result of this interaction is the recruitment of a transcriptional activator Cga1 (Candida galactose gene activator, orf19.4959) and transcription of the GAL genes proceeds. Rep1 and Cga1 are conserved across the CTG species. Rep1 itself does not possess transcriptional activity. Instead, it provides a scaffold to recruit different factors for transcriptional regulation. Rep1-Cga1 mode of regulation represents a new example of network rewiring in fungi, which provides insight into how C. albicans evolves transcriptional programs to colonize diverse host niches.

molecular biology↗

bioRxiv2022

Treatment of non-alcoholic steatohepatitis with recombinant Orosomucoid 2, an acute phase protein that attenuates the Erk1/2-PPARγ-Cd36 signaling pathway

Therapeutic administration of recombinant proteins has been used for the treatment of various diseases in multiple studies. Herein, we investigated the function of the acute phase protein Orosomucoid 2 (Orm2), which is mainly secreted by hepatocytes, and evaluated its potential as a therapeutic strategy for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). We here revealed that a high expression of Orm2 protected mice from high-fat diet (HFD)-induced obesity. The pharmacological administration of recombinant ORM2 protein attenuated hepatic steatosis, inflammation, hepatocyte injury, and fibrosis in mouse livers, which suffered NAFLD and NASH under dietary challenge conditions. Orm2 knockout mice spontaneously underwent obese after 16 weeks under normal diet. Orm2 deficiency exacerbated HFD-induced steatosis, steatohepatitis, and fibrosis in mice. Mechanistically, the deletion of Orm2 led to the activation of the Erk1/2-PPAR{gamma}-Cd36 signaling pathway, which in turn increased fatty acid uptake and absorption in hepatocytes and mice. Collectively, our results provide Orm2 is an essential factor for preventing NASH and associated NAFLD under obesity.

molecular biology↗

bioRxiv2022

Pangenome-based dynamic trajectories of intracellular gene transfers in Poaceae unveil a high rate of unceasing integration and selective retention in Triticeae

Intracellular gene transfers (IGTs) between the nucleus and organelles, including plastids and mitochondria, constantly reshapes the nuclear genome during evolution. Despite the substantial contribution of IGTs to genome variation, the dynamic trajectories of IGTs at the pangenomic level remain elusive. Here, we propose a novel approach, IGTminer, to map the evolutionary trajectories of IGTs by collinearity and gene reannotation across multiple genome assemblies. IGTminer was applied to create a nuclear organelle gene (NOG) map across 67 genomes covering 15 Poaceae species, including important crops, revealing the polymorphisms and trajectory dynamics of NOGs. The NOGs produced were verified by experimental evidence and resequencing datasets. We found that most of the NOGs were recently transferred and lineage specific, and that Triticeae species tended to have more NOGs than other Poaceae species. Wheat had a higher retention rate of NOGs than maize and rice, and the retained NOGs were likely involved in the photosynthesis and translation pathways. Large numbers of NOG clusters were aggregated in hexaploid wheat during two rounds of polyploidization and contributed to the genetic diversities among modern wheat varieties. Finally, we proposed a radiocarbon-like model illustrating the transfer and elimination dynamics of NOGs, highlighting the unceasing integration and selective retention of NOGs over evolutionary time. In addition, we implemented an interactive webserver for NOG exploration in Poaceae. In summary, this study provides new resources and clues for the roles of IGTs in shaping inter- and intraspecies genome variation and driving plant genome evolution.

evolutionary biology↗

bioRxiv2022

Improving polygenic risk prediction in admixed populations by explicitly modeling ancestral-specific effects via GAUDI

Polygenic risk scores (PRS) have shown successes in clinics, but most PRS methods have focused only on individuals with one primary continental ancestry, thus poorly accommodating recently-admixed individuals. Here, we develop GAUDI, a novel penalized-regression-based method specifically designed for admixed individuals by explicitly modeling ancestry-specific effects and jointly estimating ancestry-shared effects. We demonstrate marked advantages of GAUDI over other methods through comprehensive simulation and real data analyses.

genetics↗

bioRxiv2022

Crossing-over decision landscape in maize

In most crops, including maize, meiotic double-strand breaks (DSBs) occur in all chromosome regions but crossovers (COs) are predominantly near chromosome ends. To understand how the uniform DSB distribution changes into the U-shaped CO distribution, we generated high-resolution maps of CO intermediates. We found that DSBs with medium resection spans more often result in COs than those with shorter or longer resections. We also discovered that sites of CO intermediates associated with MLH3 in zygotene are uniformly distributed along chromosomes, resembling DSB distribution. However, in late prophase, they show the U-shaped distribution characteristic of COs. While zygotene MLH3 sites exhibit methylation levels similar to the genome average, late prophase sites have reduced DNA methylation. In contrast to DNA methylation, inter-parental DNA sequence polymorphism has limited effect on CO distribution. These data indicate that the final CO landscape shape in maize is established late during recombination and controlled by chromatin state.

plant biology↗

bioRxiv2022

SRSF2 is required for mRNA splicing and spermatogenesis

RNA splicing plays significant roles in fundamental biological activities. However, our knowledge about the roles of alternative splicing and underlying mechanisms during spermatogenesis is limited. Here, we report that Serine/arginine-rich splicing factor 2 (SRSF2), also known as SC35, plays critical roles in alternative splicing and male reproduction. Male germ cell-specific deletion of Srsf2 by Stra8-Cre caused complete infertility and defective spermatogenesis. Further analyses revealed that deletion of Srsf2 disrupted differentiation and meiosis initiation of spermatogonia. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that SRSF2 regulatory networks play critical roles in several major events including reproductive development, spermatogenesis, meiotic cell cycle, synapse organization, DNA recombination, chromosome segregation, and male sex differentiation. Furthermore, SRSF2 affected expression and alternative splicing of Stra8, Stag3 and Atr encoding critical factors for spermatogenesis in a direct manner. Taken together, our results demonstrate that SRSF2 has important functions in spermatogenesis and male fertility by regulating alternative splicing.

developmental biology↗