Co-transcriptional gene regulation in eukaryotes and prokaryotes

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(7), P. 534 - 554

Published: March 20, 2024

Language: Английский

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Regulation and function of alternative polyadenylation in development and differentiation

RNA Biology, Journal Year: 2023, Volume and Issue: 20(1), P. 908 - 925

Published: Oct. 31, 2023

Alternative processing of nascent mRNAs is widespread in eukaryotic organisms and greatly impacts the output gene expression. Specifically, alternative cleavage polyadenylation (APA) a co-transcriptional molecular process that switches site (PAS) at which mRNA cleaved, resulting isoforms with different 3'UTR length content. APA can potentially affect translation efficiency, localization, stability, seeded protein–protein interactions. naturally occurs during development cellular differentiation, around 70% human genes displaying particular tissues cell types. For example, neurons tend to express long 3'UTRs due preferential PASs more distal than other used In addition, changes mark variety pathological states, including many types cancer, are preferentially cleaved proximal PASs, causing expression short 3'UTRs. Although has been widely reported, both function mechanisms regulate choice 3'end cut sites normal pathogenic conditions still poorly understood. this review, we summarize current understanding how regulated differentiation change content affects multiple aspects With being phenomenon, advent cutting-edge scientific techniques pressing need for in-vivo studies, there never better time delve into intricate polyadenylation.

Language: Английский

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(Alternative) transcription start sites as regulators of RNA processing

Trends in Cell Biology, Journal Year: 2024, Volume and Issue: unknown

Published: March 1, 2024

Alternative transcription start site usage (ATSS) is a widespread regulatory strategy that enables genes to choose between multiple genomic loci for initiating transcription. This mechanism tightly controlled during development and often altered in disease states. In this review, we examine the growing evidence highlighting role sites (TSSs) regulation of mRNA isoform selection after We discuss how choice initiation influences RNA processing importance crosstalk cell identity organism function. also speculate on possible mechanisms underlying integration transcriptional post-transcriptional processes.

Language: Английский

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Multifactorial analysis of terminator performance on heterologous gene expression in Physcomitrella

Plant Cell Reports, Journal Year: 2024, Volume and Issue: 43(2)

Published: Jan. 21, 2024

Abstract Key message Characterization of Physcomitrella 3′UTRs across different promoters yields endogenous single and double terminators for usage in molecular pharming. The production recombinant proteins health applications accounts a large share the biopharmaceutical market. While many drugs are produced microbial mammalian systems, plants gain more attention as expression hosts to produce eukaryotic proteins. In particular, good manufacturing practice (GMP)-compliant moss ( Physcomitrium patens ) has outstanding features, such excellent genetic amenability, reproducible bioreactor cultivation, humanized protein glycosylation patterns. this study, we selected characterized novel their effects on heterologous gene expression. genome contains 53,346 unique (untranslated regions) which 7964 transcripts contain at least one intron. Over 91% exhibit than polyadenylation site, indicating prevalence alternative Physcomitrella. Out all 3′UTRs, 14 terminator candidates were via transient Dual-Luciferase assays, yielding collection performing equally high established CaMV35S, AtHSP90, NOS. High testing impact reporter levels, dependent identity positioning. Testing among NOS, PpActin5 showed an increase 1000-fold between whereas increased levels by less tenfold, demonstrating stronger effect play compared terminators. Among attributes, number sites well signals found influence performance most. Our results improve biotechnology platform further our understanding how general.

Language: Английский

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Coordination of alternative splicing and alternative polyadenylation revealed by targeted long read sequencing

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 7, 2023

Abstract Nervous system development is associated with extensive regulation of alternative splicing (AS) and polyadenylation (APA). AS APA have been extensively studied in isolation, but little known about how these processes are coordinated. Here, the coordination cassette exon (CE) Drosophila was investigated using a targeted long-read sequencing approach we call Pull-a-Long-Seq (PL-Seq). This cost-effective method uses cDNA pulldown Nanopore combined an analysis pipeline to quantify inclusion exons connection 3’ ends. Using PL-Seq, identified genes that exhibit significant differences CE depending on connectivity short versus long 3’UTRs. Genomic 3’UTR deletion found alter upstream isoforms ELAV loss differentially affected work highlights importance considering 3’UTRs when monitoring events.

Language: Английский

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mRNA initiation and termination are spatially coordinated

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 7, 2024

The expression of a precise mRNA transcriptome is crucial for establishing cell identity and function, with dozens alternative isoforms produced single gene sequence. regulation isoform usage occurs by the coordination co-transcriptional processing mechanisms across gene. Decisions involved in initiation termination underlie largest extent diversity, but little known about any relationships between decisions at both ends molecules. Here, we systematically profile joint transcription start sites (TSSs) polyadenylation (PASs) tissues species. Using short long read RNA-seq data, observe that mRNAs preferentially using upstream TSSs also tend to use PASs, congruently, downstream similarly paired. This observation suggests 5' end choice may directly influence 3' ends. Our results suggest novel "Positional Initiation-Termination Axis" (PITA), which terminal are coupled based on order they appear genome. PITA more likely encode protein domains conserved sites. strongly associated length genomic features, such enriched longer genes area devoted regions regulate or Strikingly, found than non-PITA have multiple, overlapping chromatin structural related pairing ordinally In turn, coupling fast RNA Polymerase II (RNAPII) trafficking these regions. findings indicate combination spatial kinetic couple ordinal position define isoforms.

Language: Английский

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Challenges in identifying mRNA transcript starts and ends from long-read sequencing data

Genome Research, Journal Year: 2024, Volume and Issue: 34(11), P. 1719 - 1734

Published: Nov. 1, 2024

Long-read sequencing (LRS) technologies have the potential to revolutionize scientific discoveries in RNA biology through comprehensive identification and quantification of full-length mRNA isoforms. Despite great promise, challenges remain widespread implementation LRS for RNA-based applications, including concerns about low coverage, high error, robust computational pipelines. Although much focus has been placed on defining exon composition structure with data, less careful characterization done ability assess terminal ends isoforms, specifically, transcription start end sites. Such is crucial completely delineating full molecules regulatory consequences. However, there are substantial inconsistencies both coordinates reads spanning a gene, such that often fail accurately recapitulate annotated or empirically derived molecules. Here, we describe specific identifying quantifying how these issues influence biological interpretations data. We then review recent experimental advances designed alleviate problems, ideal use cases each approach. Finally, outline anticipated developments necessary improvements from

Language: Английский

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An Integrated Database for Exploring Alternative Promoters in Animals

Scientific Data, Journal Year: 2025, Volume and Issue: 12(1)

Published: Feb. 7, 2025

Alternative promoter (AP) events, as a major pre-transcriptional mechanism, can initiate different transcription start sites to generate distinct mRNA isoforms and regulate their expression. At present, hundreds of thousands APs have been identified across human tissues, considerable number demonstrated be associated with complex traits diseases. Recent researches also proven important effects on animals. However, the landscape in animals has not fully recognized. In this study, 102,349 AP profiles from 23,077 samples 12 species were systematically characterized. We further tissue-specific investigated trait-related promoters among various species. addition, we analyzed associations between enhancer RNAs (eRNA)/transcription factors (TF) means identifying potential regulatory factors. Integrating these findings, finally developed Animal-APdb, database for searching, browsing, downloading information related Animal APs. Animal-APdb is expected serve valuable resource exploring functions mechanisms

Language: Английский

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Single-molecule m6A detection empowered by endogenous labeling unveils complexities across RNA isoforms

Molecular Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Imp/IGF2BP and Syp/SYNCRIP temporal RNA interactomes uncover combinatorial networks of regulators of Drosophila brain development

Science Advances, Journal Year: 2025, Volume and Issue: 11(6)

Published: Feb. 7, 2025

Temporal patterning of neural progenitors is an evolutionarily conserved mechanism generating diversity. In Drosophila , postembryonic neurogenesis requires the RNA binding proteins (RBPs) Imp/IGF2BP and Syp/SYNCRIP. However, how they coachieve their function not well understood. Here, we elucidate in vivo temporal interactome landscapes Imp Syp during larval brain development. bind a highly overlapping set mRNAs encoding involved neurodevelopment. We identify transcripts differentially occupied by Imp/Syp over time, featuring network known previously unknown candidate regulators that are post-transcriptionally regulated Imp/Syp. Furthermore, physical coevolutionary relationships between sites reveal combinatorial, rather than competitive, mode molecular interplay. Our study establishes framework for dissecting coregulation RBP networks as providing resource understanding fate specification.

Language: Английский

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