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Modeling of mRNA deadenylation rates reveal a complex relationship between mRNA deadenylation and decay

Agnieszka Czarnocka-Cieciura1, Jarosław Poznański2, Matti Turtola3

  • 1International Institute of Molecular and Cell Biology, Księcia Trojdena 4, 02-109, Warsaw, Poland.

The EMBO Journal
|October 11, 2024
PubMed

Insights

Complete polyadenosine tail (polyA-tail) deadenylation initiates mRNA decapping. However, ribosomal protein mRNA degradation can occur independently of deadenylation, highlighting complex regulatory relationships.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • The prevailing model posits that complete cytoplasmic polyadenosine tail (polyA-tail) deadenylation is crucial for initiating mRNA decapping and degradation.
  • Understanding the precise role and regulation of deadenylation in mRNA turnover is fundamental to gene expression control.

Purpose of the Study:

  • To investigate the necessity of complete polyA-tail deadenylation for mRNA decapping and degradation initiation.
  • To explore the relationship between deadenylation rates, mRNA decay, and functional transcript groups under various conditions.
  • To analyze the specific behavior of ribosomal protein-coding mRNAs (RPG mRNAs) during stress responses.

Main Methods:

  • Direct RNA sequencing of Saccharomyces cerevisiae (S. cerevisiae) mRNAs.
  • Utilizing chase experiments under both steady-state and stress conditions.
  • Developing a numerical model based on a modified gamma distribution function to estimate deadenylation rates.
  • Employing a simplified independent method using quantile polyA-tail values to correlate decay and deadenylation rates.

Main Results:

  • Estimated transcriptomic deadenylation rate at 10 A/min using a numerical model.
  • Demonstrated a correlation between mRNA decay and deadenylation rates, consistent within functional transcript groups and linked to codon optimality.
  • Observed variations in deadenylation and decay rates during stress response, particularly in RPG mRNAs.
  • Found that RPG mRNA degradation can proceed independently of deadenylation, contingent on nuclear export, even under heat stress.

Conclusions:

  • Reaffirmed the general primary function of deadenylation in dictating the onset of mRNA decapping.
  • Revealed complex interdependencies between deadenylation, decapping, and mRNA decay processes.
  • Highlighted the unique regulatory mechanisms governing RPG mRNA turnover, especially under stress conditions.
Keywords:
Ccr4-NOT and Pan2/3 DeadenylasesDcp2 Decapping and Xrn1 DegradationONT Nanopore Direct RNA Sequencing (DRS)Pab1mRNA Deadenylation and Degradation

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