Biology subjects

Khan, A.

Publications and source records attributed to Khan, A..

At least 199 records · Page 11Linked to original sources

bioRxiv2019

Guanidine hydrochloride reactivates an ancient septin hetero-oligomer assembly pathway in budding yeast

Septin proteins co-assemble into hetero-oligomers that polymerize into cytoskeletal filaments with a variety of cellular functions. In Saccharomyces cerevisiae, where septins were first discovered, five subunits comprise two species of septin hetero-octamers, Cdc11/Shs1-Cdc12-Cdc3-Cdc10- Cdc10-Cdc3-Cdc12-Cdc11/Shs1. Septins evolved from ancestral GTPases. We previously found evidence that slow GTPase activity by Cdc12 directs the choice of incorporation of Cdc11 vs Shs1 into septin complexes. It was unclear why many septins, including Cdc3, lack GTPase activity. We serendipitously discovered that the small molecule guanidine hydrochloride (GdnHCl) rescues septin function in cdc10 mutants by promoting assembly of non-native Cdc11/Shs1-Cdc12-Cdc3- Cdc3-Cdc12-Cdc11/Shs1 hexamers. We provide evidence that in S. cerevisiae Cdc3 guanidinium ion (Gdm) occupies the site of a "missing" Arg sidechain that is present in other fungal species in which (i) the Cdc3 subunit is an active GTPase and (ii) Cdc10-less hexamers co-exist with octamers in wild-type cells. These findings support a model in which Gdm reactivates a latent septin assembly pathway that was suppressed during fungal evolution in order to restrict assembly to hetero-octamers. Given that septin hexamers made natively in human cells also exclude Cdc10-like central subunits via homodimerization of an active GTPase, our results provide new mechanistic details that likely apply to septin assembly throughout phylogeny.

genetics↗

bioRxiv2019

Simulating individually targeted transcranial electric stimulation for experimental application

Transcranial electric stimulation (tES) induces electric fields that are subject to a complex interaction with individual anatomical properties, such as the low-conducting human skull, the distribution of cerebrospinal fluid or the sulcal depth, as well as stimulation target location and orientation. This complex interaction might contribute to the heterogenous results that are commonly observed in applications of tES in humans. Targeted tES, on the other hand, might be able to account for some of these individual factors. In the present study, we used the finite-element method (FEM) and head models of twenty-one participants to evaluate the effect of individually targeted tES on simulated intracranial current densities. Head models were based on an automated segmentation algorithm to facilitate processing in experimental sample sizes. We compared a standard stimulation montage to two individually optimized tES montages using an Alternating Direction Method of Multipliers (ADMM) and a Constrained Maximum Intensity (CMI) approach. A right parietal target was defined with three different orientations. Individual current densities showed varying intensity and spatial extent near the lower limit at which physiological efficacy of electric fields can be assumed. Both individually optimized targeting algorithms were able to control the electric field properties, with respect to intensities and/or spatial extent of the electric fields. Still, across head models, intensity in the stimulation target was constrained by individual anatomical properties. Thus, our results underline the importance of targeted tES in enhancing the effectiveness of future tES applications and in elucidating the underlying mechanisms.

neuroscience↗

bioRxiv2019

Reversible Mitochondrial Fragmentation in iPSC-Derived Cardiomyocytes from Children with DCMA, a Mitochondrial Cardiomyopathy

BackgroundThe dilated cardiomyopathy with ataxia syndrome (DCMA) is an understudied autosomal recessive disease caused by loss-of-function mutations in the poorly characterized gene DNAJC19. Clinically, DCMA is commonly associated with heart failure and early death in affected children through an unknown mechanism. DCMA has been linked to Barth syndrome, a rare but well-studied disorder caused by deficient maturation of cardiolipin (CL), a key mitochondrial membrane phospholipid.\n\nMethodsPeripheral blood mononuclear cells from two children with DCMA and severe cardiac dysfunction were reprogrammed into induced pluripotent stem cells (iPSCs). Patient and control iPSCs were differentiated into beating cardiomyocytes (iPSC-CMs) using a metabolic selection strategy and mitochondrial structure and CL content before and after incubation with the mitochondrially-targeted peptide SS-31 were quantified.\n\nResultsPatient iPSCs carry the causative DNAJC19 mutation (rs137854888) found in the Hutterite population and the iPSC-CMs demonstrated highly fragmented and abnormally-shaped mitochondria associated with an imbalanced isoform ratio of the mitochondrial protein OPA1, an important regulator of mitochondrial fusion. These abnormalities were reversible by incubation with SS-31 for 24 hours. Differentiation of iPSCs into iPSC-CMs increased the number of CL species observed but consistent, significant differences in CL content were not seen between patients and control.\n\nConclusionsWe describe a unique and novel cellular model that provides insight into the mitochondrial abnormalities present in DCMA and identifies SS-31 as a potential therapeutic for this devastating disease.

cell biology↗

bioRxiv2019

Differential detection of Entamoeba species in stool samples collected from children in District Swat, Khyber Pakhtunkhwa Pakistan

BackgroundAmoebiasis is an intestinal disease caused by enteric protozoan called Entamoeba histolytica belongs to the Genus Entamoeba. The main reason of infection is the contamination of food and water due to the poor sanitation. Among Entamoeba species, Entamoeba histolytica is highly pathogenic while the other species are non-pathogenic and needs no medical treatment.\n\nMethodologyA total of 400 stool samples were collected from different areas of district Swat and were processed for screening of amoebic cells. Microscopically identified samples containing amoebic cells were stored at -20 {degrees}C till DNA extraction. Extracted DNA was used in a PCR reaction with specific reference primers to amplify the target DNA.\n\nResultsOut of all 400 stool samples 111 (27.7%) were found positive through microscopy while PCR reaction confirmed 80 out of microscope positive samples. Among 80 PCR positive samples, the infection with Entamoeba dispar was most common (57.5%) followed by E. histolytica (47.5%) and Entamoeba moshkovskii (20%). The positive cases for mono-infection of E. dispar were 33 (41.25%), followed by E.histolytica 25 (31.25%) and E. moshkovskii 7 (8.75%). The co-infection of E. histolytica with E. dispar and E. moshkovskii was 6 (7.5%) and 2 (2.5%), respectively. Similarly the co-infection of Entamoeba dispar with Entamoeba moshkovskii was also 2 (2.5%) while 5 (6.25%) samples were observed with mixed infection of E. histolytica, E. dispar and E. moshkovskii.\n\nSignificance of the studyThe aim of the study was to detect and differentiate the E. histolytica, Entamoeba dispar and Entamoeba moshkovskii using conventional microscopy and polymerase chain reaction. The results suggested that the use of PCR is necessary to differentiate E. histolytica from E. dispar and E. moshkovskii and therefore, to avoid unnecessary treatment the present study recommend the use of PCR for the routine diagnosis of amoebiasis in the study area. It is also suggested that further studies from this area may also facilitate the understanding of genetic diversity of these pathogens.

microbiology↗

bioRxiv2019

Is shed hair the most effective non-invasive resource for estimating wild pedigrees?

Wild pedigrees are critical for better understanding mating systems and inbreeding scenarios to inform conservation strategies for endangered species. To delineate pedigrees in wild populations, many identified individuals will have to be genotyped at thousands of loci, mostly from non-invasive samples. This requires us to quantify (a) the most common non-invasive sample available from identified individuals (b) the ability to acquire genome-wide data from such samples, and (c) the quality of such genome-wide data, and its ability to reconstruct relationships between animals within a population. We followed identified individuals from a wild endangered tiger population, and found that shed hair samples were most common compared to fecal samples, carcasses and opportunistic invasive samples. DNA extraction, library preparation and whole genome sequencing resulted in between 126,129 and 512,689 SNPs from across the genome for four such samples. Exploratory population genetic analyses revealed that these data were free of holistic biases, and could recover expected population structure and relatedness. Mitochondrial genomes recovered matrilineages as suggested by long-term monitoring data. Even with these few samples, we were able to uncover the matrilineage for an individual with unknown ancestry. In summary, we demonstrated that non-invasive shed hair samples yielded adequate quality/quantity DNA AND in conjunction with sensitive library preparation methods, provided reliable data from hundreds of thousands of SNPs across the genome. This makes shed hair are an effective resource for studying individual-based genetics of elusive endangered species.

genomics↗

bioRxiv2019

Genomic Influences on Self-Reported Childhood Maltreatment

Childhood maltreatment is highly prevalent and serves as a risk factor for mental and physical disorders. Self-reported childhood maltreatment appears heritable, but the specific genetic influences on this phenotype are largely unknown. The aims of this study were to 1) identify genetic variation associated with reported childhood maltreatment, 2) calculate the relevant SNP-based heritability estimates, and 3) quantify the genetic overlap of reported childhood maltreatment with mental and physical health-related phenotypes. Genome-wide association analysis for childhood maltreatment was undertaken, using a discovery sample from the UK Biobank (UKBB) (n=124,000) and a replication sample from the Psychiatric Genomics Consortium-posttraumatic stress disorder working group (PGC-PTSD) (n=26,290). Heritability estimations for childhood maltreatment and genetic correlations with mental/physical health traits were calculated using linkage disequilibrium score regression (LDSR). Two genome-wide significant loci associated with childhood maltreatment, located on chromosomes 3p13 (rs142346759, beta=0.015, p=4.35x10-8, FOXP1) and 7q31.1 (rs10262462, beta=-0.016, p=3.24x10-8, FOXP2), were identified in the discovery dataset but were not replicated in the PGC-PTSD sample. SNP-based heritability for childhood maltreatment was estimated to be [~]6%. Childhood maltreatment was most significantly genetically correlated with depressive symptoms (rg=0.70, p=4.65x10-40). This is the first large-scale genetic study to identify specific variants associated with self-reported childhood maltreatment. FOXP genes could influence traits such as depression and thereby be relevant to childhood maltreatment. Alternatively, these variants may be associated with a greater likelihood of reporting maltreatment. A clearer understanding of the genetic relationships of childhood maltreatment, including particular abuse subtypes, with various psychiatric disorders, may ultimately be useful in in developing targeted treatment and prevention strategies.

genomics↗

bioRxiv2019

Recent evolutionary history of tigers highlights contrasting roles of genetic drift and selection

Formulating strategies for species conservation requires knowledge of evolutionary and genetic history. Tigers are among the most charismatic of endangered species and garner significant conservation attention. However, the evolutionary history and genomic variation of tigers remain poorly known. With 70% of the worlds wild tigers living in India, such knowledge is critical for tiger conservation. We re-sequenced 65 individual tiger genomes across their extant geographic range, representing most extant subspecies with a specific focus on tigers from India. As suggested by earlier studies, we found strong genetic differentiation between the putative tiger subspecies. Despite high total genomic diversity in India, individual tigers host longer runs of homozygosity, potentially suggesting recent inbreeding, possibly because of small and fragmented protected areas. Surprisingly, demographic models suggest recent divergence (within the last 10,000 years) between populations, and strong population bottlenecks. Amur tiger genomes revealed the strongest signals of selection mainly related to metabolic adaptation to cold, while Sumatran tigers show evidence of evolving under weak selection for genes involved in body size regulation. Depending on conservation objectives, our results support the isolation of Amur and Sumatran tigers, while geneflow between Malayan and South Asian tigers may be considered. Further, the impacts of ongoing connectivity loss on the health and persistence of tigers in India should be closely monitored.

genomics↗

bioRxiv2019

Unraveling the hexaploid sweetpotato inheritance using ultra-dense multilocus mapping

The hexaploid sweetpotato (Ipomoea batatas (L.) Lam., 2n = 6x = 90) is an important staple food crop worldwide and has a vital role in alleviating famine in developing countries. Due to its high ploidy level, genetic studies in sweetpotato lag behind major diploid crops significantly. We built an ultra-dense multilocus integrated genetic map and characterized the inheritance system in a sweetpotato full-sib family using our newly implemented software, MAPpoly. The resulting genetic map revealed 96.5% collinearity between I. batatas and its diploid relative I. trifida. We computed the genotypic probabilities across the whole genome for all individuals in the mapping population and inferred their complete hexaploid haplotypes. We provide evidence that most of the meiotic configurations (73.3%) were resolved in bivalents, although a small portion of multivalent signatures (15.7%), among other inconclusive configurations (11.0%) were also observed. Except for low levels of preferential pairing in linkage group 2, we observed a hexasomic inheritance mechanism in all linkage groups. We propose that the hexasomic-bivalent inheritance promotes stability to the allelic transmission in sweetpotato.

genetics↗

bioRxiv2019

Gene Loss and Evolution of the Plastome

Chloroplasts are unique organelles within the plant cells and are responsible for sustaining life forms on the earth due to their ability to conduct photosynthesis. Multiple functional genes within the chloroplast are responsible for a variety of metabolic processes that occur in the chloroplast. Considering its fundamental role in sustaining life on the earth, it is important to identify the level of diversity present in the chloroplast genome, what genes and genomic content have been lost, what genes have been transferred to the nuclear genome, duplication events, and the overall origin and evolution of the chloroplast genome. Our analysis of 2511 chloroplast genomes indicated that the genome size and number of coding DNA sequences (CDS) in the chloroplasts genome of algae are higher relative to other lineages. Approximately 10.31% of the examined species have lost the inverted repeats (IR) in the chloroplast genome that span across all the lineages. Genome-wide analyses revealed the loss of the Rbcl gene in parasitic and heterotrophic plants occurred approximately 56 Ma ago. PsaM, Psb30, ChlB, ChlL, ChlN, and Rpl21 were found to be characteristic signature genes of the chloroplast genome of algae, bryophytes, pteridophytes, and gymnosperms; however, none of these genes were found in the angiosperm or magnoliid lineage which appeared to have lost them approximately 203-156 Ma ago. A variety of chloroplast-encoded genes were lost across different species lineages throughout the evolutionary process. The Rpl20 gene, however, was found to be the most stable and intact gene in the chloroplast genome and was not lost in any of the analyzed species, suggesting that it is a signature gene of the plastome. Our evolutionary analysis indicated that chloroplast genomes evolved from multiple common ancestors ~1293 Ma ago and have undergone vivid recombination events across different taxonomic lineages.

plant biology↗

bioRxiv2019

SS-31 Reverses Mitochondrial Fragmentation in Fibroblasts from Patients with DCMA, a Mitochondrial Cardiomyopathy

ObjectivesWe used patient dermal fibroblasts to characterize the mitochondrial abnormalities associated with the dilated cardiomyopathy with ataxia syndrome (DCMA) and to study the effect of the mitochondrially-targeted peptide SS-31 as a potential novel therapeutic.\n\nBackgroundDCMA is an understudied autosomal recessive disorder thought to be related to Barth syndrome but caused by mutations in DNAJC19, a protein of unknown function localized to the mitochondria. The clinical disease is characterized by 3-methylglutaconic aciduria, dilated cardiomyopathy, abnormal neurological development and other heterogeneous features. Until recently no effective therapies had been identified and affected patients frequently died in early childhood from intractable heart failure.\n\nMethodsDermal fibroblasts from four pediatric patients with DCMA were used to establish parameters of mitochondrial dysfunction. Mitochondrial structure, reactive oxygen species (ROS) production, cardiolipin composition and gene expression were evaluated.\n\nResultsImmunocytochemistry with semi-automated quantification of mitochondrial structural metrics and transmission electron microscopy demonstrated mitochondria to be highly fragmented in DCMA fibroblasts compared to healthy control cells. Live-cell imaging demonstrated significantly increased ROS production in patient cells. These structural and functional abnormalities were reversed by treating DCMA fibroblasts with SS-31, a synthetic peptide that localizes to the inner mitochondrial membrane. Levels of cardiolipin were not significantly different between control and DCMA cells and were unaffected by SS-31 treatment.\n\nConclusionsOur results demonstrate the abnormal mitochondrial structure and function in fibroblasts from patients with DCMA and suggest that SS-31 may represent a potential therapy for this devastating disease.

cell biology↗

bioRxiv2019

Multiple QTL mapping in autopolyploids: a random-effect model approach with application in a hexaploid sweetpotato full-sib population

In developing countries, the sweetpotato, Ipomoea batatas (L.) Lam. (2n = 6x = 90), is an important autopolyploid species, both socially and economically. However, quantitative trait loci (QTL) mapping has remained limited due to its genetic complexity. Current fixed-effect models can only fit a single QTL and are generally hard to interpret. Here we report the use of a random-effect model approach to map multiple QTL based on score statistics in a sweetpotato bi-parental population ( Beauregard x Tanzania) with 315 full-sibs. Phenotypic data were collected for eight yield component traits in six environments in Peru, and jointly predicted means were obtained using mixed-effect models. An integrated linkage map consisting of 30,684 markers distributed along 15 linkage groups (LGs) was used to obtain the genotype conditional probabilities of putative QTL at every cM position. Multiple interval mapping was performed using our R package QTLPOLY and detected a total of 41 QTL, ranging from one to ten QTL per trait. Some regions, such as those on LGs 3 and 15, were consistently detected among root number and yield traits and provided basis for candidate gene search. In addition, some QTL were found to affect commercial and noncommercial root traits distinctly. Further best linear unbiased predictions allowed us to characterize additive allele effects as well as to compute QTL-based breeding values for selection. Together with quantitative genotyping and its appropriate usage in linkage analyses, this QTL mapping methodology will facilitate the use of genomic tools in sweetpotato breeding as well as in other autopolyploids.

genetics↗

bioRxiv2019

Genomics, Molecular and Evolutionary Perspective of NAC Transcription Factors

NAC (NAM, ATAF1,2, and CUC2) transcription factors are one of the largest transcription factor families found in plants and are involved in diverse developmental and signalling events. Despite the availability of comprehensive genomic information from diverse plant species, the basic genomic, biochemical, and evolutionary details of NAC TFs have not been established. Therefore, NAC TFs family proteins from 160 plant species were analyzed in the current study. The analysis, among other things, identified the first algal NAC TF in the Charophyte, Klebsormidium flaccidum. Furthermore, our analysis revealed that NAC TFs are membrane bound and contain monopartite, bipartite, and multipartite nuclear localization signals. NAC TFs were also found to encode a novel chimeric protein domain and are part of a complex interactome network. Synonymous codon usage is absent in NAC TFs and it appears that they have evolved from orthologous ancestors and undergone significant duplication events to give rise to paralogous NAC TFs.

genomics↗

bioRxiv2019

Hippocampal morphology and cytoarchitecture in the 3D BigBrain

The internal structure of the human hippocampus is challenging to map using histology or neuroimaging due to its complex archicortical folding. Here, we aimed to overcome this challenge using a unique combination of three methods. First, we leveraged a histological dataset with unprecedented 3D coverage, 3D BigBrain. Second, we imposed a computational unfolding framework that respects the topological continuity of hippocampal subfields, which are traditionally defined by laminar composition. Third, we adapted neocortical parcellation techniques to map the hippocampus with respect to not only laminar but also morphological features. Unsupervised clustering of these features revealed subdivisions that closely resemble ground-truth manual subfield segmentations. Critically, we also show that morphological features alone are sufficient to derive most hippocampal subfield boundaries. Moreover, some features showed differences within subfields along the hippocampal longitudinal axis. Our findings highlight new characteristics of internal hippocampal structure, and offer new avenues for its characterization with in-vivo neuroimaging.

neuroscience↗

bioRxiv2019

Extremely Drug-Resistant Pseudomonas aeruginosa ST309 Harboring Tandem GES Enzymes: A Newly Emerging Threat in the United States

Two ST309 Pseudomonas aeruginosa clinical isolates resistant to carbapenems and newer {beta}-lactam/{beta}-lactamase inhibitor combinations were found to harbor the extended spectrum beta-lactamases GES 19 and 26 genetically clustered in tandem. The combination of ceftazidime/avibactam plus aztreonam achieved cure in one patient. Phylogenetic analysis suggests that ST309 P. aeruginosa carrying tandem GES are an emerging lineage in the United States.

microbiology↗

bioRxiv2019

Comparative analysis of mitochondrial genome between UG93A and UG93B reveal common feature of 5’-end heterogeneity in mitochondrial genes of kenaf

Plant cytoplasmic male sterility (CMS) being maternal phenomenon trait that result from pollen abortion and closely linked with mitochondrial DNA rearrangement in many crops including kenaf. However, the molecular mechanism in kenaf is poorly known. In present work, we described the mitochondrial genome in isonuclear CMS line UG93A and its maintainer line UG93B. Findings of the current study revealed that a total of 398 SNPs and 230 InDels were identified in UG93A mtDNA. Total of 26 SNPs variations and three InDels were identified in the coding region of atp6, indicating its active role in mitochondrial genome re-arrangement. Northern blot analysis showed that the transcripts of atp1, atp4, atp6, cox3 and sdh4 in F1 were consistent with UG93A but different for UG93B. The transcript of atp9 was found similar between UG93B and F1 while different for UG93A, which depict that atp9 may be regulated by nuclear genes in F1 hybrid. The expression of atp9 in UG93A was substantially lower compared with UG93B, suggesting its key role for energy supplying in microspore development of kenaf. Circularized RNA (CR)-RT-PCR revealed that mitochondrial RNAs with heterogeneous 5-ends but uniform 3 - ends are common feature in kenaf mitochondrial genes, and the promoter architecture analysis showed that the promoter sequences in kenaf mitochondrial genome are highly diverged in comparison to those in other plants. Our data highlight that the translation of mitochondrial genes in kenaf is closely associated with heterogeneity of the 5-end of plant mRNA. The present result provides the basic information in understanding the transcription of kenaf mitochondrial genome and can be used as reference in other plants.

molecular biology↗

bioRxiv2019

Exaggerated in vivo IL-17 responses discriminate recall responses in active TB

Host immune responses at the site of Mycobacterium tuberculosis (Mtb) infection serve to contain the pathogen, but also mediate the pathogenesis of tuberculosis (TB) and onward transmission of infection. Interferon gamma (IFN{gamma}) responses do not discriminate between protection and pathogenicity, but IL-17A/F responses, known to drive pathology in diverse chronic inflammatory diseases, have also been associated with TB pathogenesis in animal models. At the site of in vivo immune recall responses to Mtb modelled by the tuberculin skin test, we show for the first time that active TB in humans is also associated with exaggerated IL-17A/F expression, accumulation of Th17 cells and IL-17A/F bioactivity, including increased neutrophil recruitment and matrix metalloproteinase-1 expression directly implicated in TB pathogenesis. These features discriminate recall responses in patients with active TB from those with cured or latent infection and are also evident at the site of TB disease. Our data support targeting of this pathway in host-directed therapy for TB.

immunology↗

bioRxiv2018

Cohort Profile: East London Genes & Health (ELGH), a community based population genomics and health study in people of British-Bangladeshi and -Pakistani heritage.

Cohort profile in a nutshellO_LIEast London Genes & Health (ELGH) is a large scale, community genomics and health study (to date >34,000 volunteers; target 100,000 volunteers). C_LIO_LIELGH was set up in 2015 to gain deeper understanding of health and disease, and underlying genetic influences, in British-Bangladeshi and British-Pakistani people living in east London. C_LIO_LIELGH prioritises studies in areas important to, and identified by, the community it represents. Current priorities include cardiometabolic diseases and mental illness, these being of notably high prevalence and severity. However studies in any scientific area are possible, subject to community advisory group and ethical approval. C_LIO_LIELGH combines health data science (using linked UK National Health Service (NHS) electronic health record data) with exome sequencing and SNP array genotyping to elucidate the genetic influence on health and disease, including the contribution from high rates of parental relatedness on rare genetic variation and homozygosity (autozygosity), in two understudied ethnic groups. Linkage to longitudinal health record data enables both retrospective and prospective analyses. C_LIO_LIThrough Stage 2 studies, ELGH offers researchers the opportunity to undertake recall-by-genotype and/or recall-by-phenotype studies on volunteers. Sub-cohort, trial-within-cohort, and other study designs are possible. C_LIO_LIELGH is a fully collaborative, open access resource, open to academic and life sciences industry scientific research partners. C_LI

genomics↗

bioRxiv2018

Modeling RNA-binding protein specificity in vivo by precisely registering protein-RNA crosslink sites

RNA-binding proteins (RBPs) regulate post-transcriptional gene expression by recognizing short and degenerate sequence elements in their target transcripts. Despite the expanding list of RBPs with in vivo binding sites mapped genomewide using crosslinking and immunoprecipitation (CLIP), defining precise RBP binding specificity remains challenging. We previously demonstrated that the exact protein-RNA crosslink sites can be mapped using CLIP data at single-nucleotide resolution and observed that crosslinking frequently occurs at specific positions in RBP motifs. Here we have developed a computational method, named mCross, to jointly model RBP binding specificity while precisely registering the crosslinking position in motif sites. We applied mCross to 112 RBPs using ENCODE eCLIP data and validated the reliability of the resulting motifs by genome-wide analysis of allelic binding sites also detected by CLIP. We found that the prototypical SR protein SRSF1 recognizes GGA clusters to regulate splicing in a much larger repertoire of transcripts than previously appreciated.

molecular biology↗