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Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
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In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
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RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
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Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
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Identification of Alternative Splicing and Polyadenylation in RNA-seq Data
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Alternative polyadenylation regulation: insights from sequential polyadenylation.

Peng Tang1, Yu Zhou1,2

  • 1State Key Laboratory of Virology, College of Life Sciences, RNA Institute, Wuhan University, Wuhan, P. R. China.

Transcription
|August 25, 2022
PubMed
Summary

Alternative polyadenylation (APA) processing may involve sequential activation of proximal sites after distal ones, challenging the traditional view. This suggests a multi-cleavage mechanism for regulating gene expression via messenger RNA processing.

Keywords:
APAAlternative polyadenylationregulationsequential polyadenylation

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Alternative polyadenylation (APA) is crucial for gene expression regulation.
  • APA site processing was traditionally considered independent events on pre-mRNAs.

Approach:

  • Review of established APA regulatory mechanisms.
  • Discussion of sequential polyadenylation insights.
  • Development of a unified leverage model for APA regulation.

Key Points:

  • Recent findings indicate proximal APA sites can activate sequentially after distal sites.
  • This challenges the canonical one-cleavage-per-transcript model.
  • A multi-cleavage-same-transcript mode is proposed.

Conclusions:

  • A unified model integrating sequential polyadenylation provides new understanding of regulated APA.
  • This perspective reconciles previous observations and offers a broader framework for APA research.