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Widespread intron retention in mammals functionally tunes transcriptomes.

Ulrich Braunschweig1, Nuno L Barbosa-Morais2, Qun Pan1

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Summary
This summary is machine-generated.

Intron retention (IR), a form of alternative splicing, is surprisingly common in mammals. This process helps regulate gene expression by reducing the levels of unneeded transcripts, acting as a crucial transcriptome tuning mechanism.

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Area of Science:

  • Molecular Biology
  • Genomics
  • RNA Biology

Background:

  • Alternative splicing (AS) significantly expands the functional capacity of eukaryotic genomes.
  • Intron retention (IR) is the least understood form of AS, prevalent in plants but considered rare in animals.
  • Previous studies underestimated the prevalence of IR in mammalian transcriptomes.

Purpose of the Study:

  • To investigate the prevalence and function of intron retention (IR) in mammalian transcriptomes.
  • To identify sequence features and mechanisms regulating IR.
  • To elucidate the role of IR in transcriptome regulation and gene expression control.

Main Methods:

  • Analysis of high-coverage poly(A)(+) RNA-seq data from mammalian samples.
  • Identification and characterization of cis-acting sequence features ('IR code') associated with intron retention.
  • Investigation of the functional consequences of IR, including its impact on transcript levels and cellular physiology.

Main Results:

  • Intron retention (IR) is unexpectedly frequent in mammals, affecting up to 75% of multiexonic genes.
  • A specific set of cis-acting features, termed the 'IR code', accurately predicts retained introns.
  • IR functions to "tune" transcript levels, reducing expression of non-essential transcripts via nonsense-mediated decay and nuclear sequestration.
  • IR is linked to RNA polymerase II (Pol II) stalling and reduced spliceosomal component availability.

Conclusions:

  • Intron retention is a widespread and significant mechanism for transcriptome regulation in mammals.
  • The 'IR code' provides insights into the regulation of intron retention.
  • IR acts as a global checkpoint to suppress inappropriate gene expression through coordinated Pol II pausing and splicing regulation.