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MicroRNAs Cause Accelerated Decay of Short-Tailed Target mRNAs

Timothy J Eisen1, Stephen W Eichhorn1, Alexander O Subtelny1

  • 1Howard Hughes Medical Institute, Cambridge, MA 02142, USA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Molecular Cell
|January 7, 2020
PubMed

Insights

MicroRNAs (miRNAs) accelerate deadenylation and decay of target mRNAs. This dual action prevents significant changes in mRNA poly(A)-tail length distribution at steady state.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Post-transcriptional Modification

Background:

  • MicroRNAs (miRNAs) are key regulators of gene expression.
  • miRNAs recruit deadenylases to target messenger RNAs (mRNAs).
  • The impact of miRNAs on mRNA poly(A)-tail dynamics at steady state is not fully understood.

Purpose of the Study:

  • To investigate the pre-steady-state effects of miRNAs on mRNA tail lengths, levels, and translational efficiencies.
  • To elucidate the mechanisms by which miRNAs influence mRNA fate.
  • To computationally model the observed phenomena.

Main Methods:

  • Measurement of pre-steady-state changes in poly(A)-tail lengths, mRNA levels, and translational efficiencies.
  • Application of computational modeling to analyze miRNA-mediated mRNA decay pathways.

Main Results:

  • miRNAs minimally affect translational efficiency compared to mRNA levels.
  • Effects on mRNA levels accumulate over time, while effects on tail lengths peak early and then decrease.
  • miRNAs induce accelerated deadenylation and accelerated decay of short-tailed mRNA molecules.

Conclusions:

  • miRNAs exhibit a dual role in regulating target mRNA turnover.
  • Accelerated decay of short-tailed mRNAs counteracts accelerated deadenylation, maintaining near-normal steady-state tail-length distributions.
  • This mechanism ensures efficient mRNA degradation without drastic alterations in poly(A)-tail length homeostasis.
Keywords:
5-ethynyl uridinePAL-seqdeadenylation ratesdecapping ratesmetabolic labelingmicroRNA mechanismpoly(A)-tail lengthsribosome footprint profiling

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