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Cited by 99RNA Research and SplicingRNA and protein synthesis mechanismsRNA regulation and disease

Perfect timing: splicing and transcription rates in living cells

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Alpert, Tara, Herzel, Lydia, Neugebauer, Karla M.·2017·WIREs RNA
DOI 10.1002/wrna.1401PMC PMC5355006
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Abstract

An important step toward understanding gene regulation is the elucidation of the time necessary for the completion of individual steps. Measurement of reaction rates can reveal potential nodes for regulation. For example, measurements of in vivo transcription elongation rates reveal regulation by DNA sequence, gene architecture, and chromatin. Pre‐mRNA splicing is regulated by transcription elongation rates and vice versa, yet the rates of RNA processing reactions remain largely elusive. Since the 1980s, numerous model systems and approaches have been used to determine the precise timing of splicing in vivo. Because splicing can be co‐transcriptional, the position of Pol II when splicing is detected has been used as a proxy for time by some investigators. In addition to these ‘distance‐based’ measurements, ‘time‐based’ measurements have been possible through live cell imaging, metabolic labeling of RNA, and gene induction. Yet splicing rates can be convolved by the time it takes for transcription, spliceosome assembly and spliceosome disassembly. The variety of assays and systems used has, perhaps not surprisingly, led to reports of widely differing splicing rates in vivo. Recently, single molecule RNA‐seq has indicated that splicing occurs more quickly than previously deduced. Here we comprehensively review these findings and discuss evidence that splicing and transcription rates are closely coordinated, facilitating the efficiency of gene expression. On the other hand, introduction of splicing delays through as yet unknown mechanisms provide opportunity for regulation. More work is needed to understand how cells optimize the rates of gene expression for a range of biological conditions. WIREs RNA 2017, 8:e1401. doi: 10.1002/wrna.1401 This article is categorized under: RNA-Based Catalysis > RNA Catalysis in Splicing and Translation RNA Interactions with Proteins and Other Molecules > RNA–Protein Complexes RNA Processing > Splicing Mechanisms

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  • Both transcription and translation are strongly affected by exact DNA and mRNA sequences, respectively, as well as their cellular environments.

    “Both transcription and translation are strongly affected by exact DNA and mRNA sequences, respectively, as well as their cellular environments (Sonenberg and Hinnebusch, 2009; Alpert et al., 2017).”

    From Evaluating Efficiencies of Dual AAV Approaches for Retinal Targeting (2017) · cites this paper as Alpert et al., 2017

    The Abstract states that DNA sequence, gene architecture, and chromatin regulate transcription elongation rates; the Introduction also discusses cell signaling and environmental cues as possible constraints. The paper does not address whether mRNA sequence or cellular environment strongly affects translation, so it supports the transcription part but not the full sentence attributed to it. (LLM, conf=0.87)

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Sorted by citations

Authors
Alpert, T., Herzel, L., & Neugebauer, K. M.
Affiliations
Yale University (US)
Corresponding author
Neugebauer, Karla M.
ORCID
Venue
WIREs RNA
Publisher
Wiley
Published
2016-11-21
Volume
8
Issue
2
ISSN
  • 1757-7004 (ISSN-L)
  • 1757-7012
DOI
10.1002/wrna.1401
PMC
PMC5355006
OpenAlex
W2556628421
Cited by
99
References
7
Citations by year
2026: 5 · 2025: 6 · 2024: 15 · 2023: 10 · 2022: 15 · 2021: 9 · 2020: 16 · 2019: 10 · 2018: 5 · 2017: 8
FWCI
0.69
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Wiley Interdisciplinary Reviews - RNA (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of General Medical Sciences (NIH R01 GM112766)
  • National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
pre-mRNA splicing, transcription elongation, co-transcriptional splicing, gene expression regulation, RNA polymerase II, spliceosome assembly, live-cell imaging
MeSH terms
Animals, Cell Survival, Chromatin, Humans, RNA Polymerase II, RNA Splicing, Time Factors, Transcription, Genetic, Spliceosomes

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