Pumilio differentially binds to mRNA 3′ UTR isoforms to regulate localization of synaptic proteins

EMBO Reports, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

Language: Английский

---

Re-appraising the evidence for the source, regulation and function of p53-family isoforms

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 52(20), P. 12112 - 12129

Published: Oct. 15, 2024

The p53 family of proteins evolved from a common ancestor into three separate genes encoding that act as transcription factors with distinct cellular roles. Isoforms each member lack specific regions or domains are suggested to result alternative start sites, splicing translation initiation, and have the potential exponentially increase functional repertoire gene. However, evidence supporting presence individual protein variants at levels is often limited inferred by mRNA detection using highly sensitive amplification techniques. We provide critical appraisal current for origins, expression, functions regulation p53-family isoforms. conclude despite wealth publications, several putative isoforms remain poorly established. Future research improved technical approaches generation isoform-specific reagents required establish physiological relevance in health disease. In addition, our analyses suggest partly through convergent rather than divergent evolution ancestral

Language: Английский

---

Understanding isoform expression by pairing long-read sequencing with single-cell and spatial transcriptomics

Genome Research, Journal Year: 2024, Volume and Issue: 34(11), P. 1735 - 1746

Published: Nov. 1, 2024

RNA isoform diversity, produced via alternative splicing, and usage of transcription start poly(A) sites, results in varied transcripts being derived from the same gene. Distinct isoforms can play important biological roles, including by changing sequences or expression levels protein products. The first single-cell approaches to sequencing—and later, spatial approaches—which are now widely used for identification differentially expressed genes, rely on short reads offer ability transcriptomically compare different cell types but limited their measure differential expression. More recently, long-read sequencing methods have been combined with technologies order characterize In this review, we provide an overview emergence discuss challenges associated implementation these interpretation data. We opportunities they understanding relationships between distinct variable elements transcript molecules highlight some ways which isoforms’ roles development pathology. Single-nucleus sequencing, a special case approach, is also discussed. attempt cover both limitations significant potential expanding our still-limited isoforms.

Language: Английский

---

Causal role of a promoter polymorphism in natural variation of the Arabidopsis floral repressor gene FLC

Current Biology, Journal Year: 2023, Volume and Issue: 33(20), P. 4381 - 4391.e3

Published: Sept. 19, 2023

Noncoding polymorphism frequently associates with phenotypic variation, but causation and mechanism are rarely established. single-nucleotide polymorphisms (SNPs) characterize the major haplotypes of Arabidopsis thaliana floral repressor gene FLOWERING LOCUS C (FLC). This noncoding generates a range FLC expression levels, determining requirement for response to winter cold. The adaptive determinant these was shown be autumnal levels expression. Here, we investigate how SNPs influence transcriptional output. We identify an upstream transcription start site (uTSS) cluster at FLC, whose usage is increased by A variant promoter SNP-230. present in relatively few accessions, majority containing G this site. demonstrate causal role -230 reduced upregulates redundantly activator FRIGIDA (FRI). additive interaction SNP-230 intronic SNP+259, which also differentially influences uTSS usage. Combinatorial interactions between activators thus generate quantitative variation that has facilitated adaptation accessions distinct climates.

Language: Английский

---

Regulation of alternative splicing and polyadenylation in neurons

Life Science Alliance, Journal Year: 2023, Volume and Issue: 6(12), P. e202302000 - e202302000

Published: Oct. 4, 2023

Cell-type–specific gene expression is a fundamental feature of multicellular organisms and achieved by combinations regulatory strategies. Although cell-restricted transcription perhaps the most widely studied mechanism, co-transcriptional post-transcriptional processes are also central to spatiotemporal control functions. One general category involves generation multiple transcript isoforms from an individual gene, whose balance cell specificity frequently tightly regulated via diverse The nervous system makes particularly extensive use cell-specific isoforms, specializing neural function genes that expressed more broadly. Here, we review strategies RNA-binding proteins direct neural-specific isoform processing. These include various classes alternative splicing polyadenylation events, both which broadly diversify transcriptome. Importantly, global alterations characteristic many pathologies, recent genetic studies demonstrate how misregulation can directly cause mutant phenotypes.

Language: Английский

---

A compendium of genetic variations associated with promoter usage across 49 human tissues

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 9, 2024

Promoters play a crucial role in regulating gene transcription. However, our understanding of how genetic variants influence alternative promoter selection is still incomplete. In this study, we implement framework to identify that affect the relative usage promoters, known as quantitative trait loci (puQTLs). By constructing an atlas human puQTLs across 49 different tissues from 838 individuals, have identified approximately 76,856 independent associated with usage, encompassing 602,009 variants. Our study demonstrates represent distinct type molecular loci, effectively uncovering regulatory targets and patterns. Furthermore, are tissue-specific manner enriched binding sites epigenetic marks transcription factors, especially those involved chromatin architecture formation. Notably, also found colocalize complex traits or diseases contribute their heritability. Collectively, findings underscore significant elucidating mechanisms underlying tissue development diseases.

Language: Английский

---

Stress responses of plants through transcriptome plasticity by mRNA alternative polyadenylation

Molecular Horticulture, Journal Year: 2023, Volume and Issue: 3(1)

Published: Sept. 28, 2023

Abstract The sessile nature of plants confines their responsiveness to changing environmental conditions. Gene expression regulation becomes a paramount mechanism for adjust physiological and morphological behaviors. Alternative polyadenylation (APA) is known its capacity augment transcriptome diversity plasticity, thereby furnishing an additional set tools modulating gene expression. APA has also been demonstrated exhibit intimate associations with plant stress responses. In this study, we review dynamic features consequences in subjected both biotic abiotic stresses. These stresses include adverse stresses, pathogenic attacks, such as cadmium toxicity, high salt, hypoxia, oxidative stress, cold, heat shock, along bacterial, fungal, viral infections. We analyzed the overarching research framework employed elucidate response alignment site transitions modulation levels within ambit each condition. proposed general model where transacting factors, including poly(A) epigenetic regulators, RNA m 6 A modification phase separation proteins, assume pivotal roles related plasticity during plants. Graphical

Language: Английский

---

Size fractionated NET‐Seq reveals a conserved architecture of transcription units around yeast genes

Yeast, Journal Year: 2024, Volume and Issue: 41(4), P. 222 - 241

Published: March 3, 2024

Abstract Genomes from yeast to humans are subject pervasive transcription. A single round of transcription is sufficient alter local chromatin conformation, nucleosome dynamics and gene expression, but hard distinguish background signals. Size fractionated native elongating transcript sequencing (sfNET‐Seq) was developed precisely map nascent transcripts independent expression levels. RNAPII‐associated fractionation into different size ranges before library construction. When anchored the start sites (TSS) annotated genes, combined pattern output metagenes gives expected reference pattern. Bioinformatic matching identified 9542 units in Saccharomyces cerevisiae , which 47% coding 53% noncoding. In total, 3113 (33%) unannotated noncoding units. Anchoring all TSS or polyadenylation site (PAS) genes reveals distinctive architectures linked pairs divergent approximately 200nt apart. The Reb1 factor enriched 30nt downstream PAS only when an upstream (TSS −60nt with respect PAS) unit co‐occurs a +150nt) acts limit levels antisense transcripts. potential for extensive transcriptional interference evident low abundance variable (median −240nt) initiating within 500nt window of, transcribing over, promoters protein‐coding genes. This study confirms highly interleaved genome types altering landscape ways, exert regulatory control.

Language: Английский

---

Geneapp: A web application for visualizing alternative splicing for biomedicine

Computers in Biology and Medicine, Journal Year: 2024, Volume and Issue: 178, P. 108789 - 108789

Published: June 26, 2024

Language: Английский

---

Neuronal RNA processing: cross-talk between transcriptional regulation and RNA-binding proteins

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Aug. 1, 2024

In the nervous system, alternative RNA processing is particularly prevalent, which results in expression of thousands transcript variants found no other tissue. Neuron-specific RNA-binding proteins co-transcriptionally regulate splicing, polyadenylation, and editing, thereby shaping identity system cells. Recent evidence suggests that interactions between cis-regulatory elements such as promoters enhancers play a role determination neuron-specific profiles. Here, we discuss possible mechanisms through transcription cross-talk to generate uniquely complex neuronal transcriptome, with focus on 3′-end formation.

Language: Английский

---