Mathematical Modeling of mRNA Poly(A) Tail Shortening Process

Methods Mol Biol. 2024:2723:303-317. doi: 10.1007/978-1-0716-3481-3_18.

Abstract

A sequence of deadenylation events, or the shortening of the poly(A) tail, is a highly regulated process during the life cycle of mRNAs. Advances in biochemistry have enabled the study of deadenylation events at single-nucleotide resolution. Here we describe mathematical models and their applications to estimate the kinetics of a single deadenylation event in vitro. We demonstrate how this quantitative approach is used for assessing reactions with synthetic RNA with poly(A) tails and the CCR4-NOT complex. This method is also applicable to investigating the catalytic activities of other exonucleases and RNA substrates. All example data and custom software are available on GitHub: https://github.com/2yngsklab/deadenylation-kinetics .

Keywords: CAF1; CCR4; CCR4-NOT; Deadenylation; Exonuclease; Poly(A) tail; RNA modification; RNA stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Exonucleases*
  • Exoribonucleases* / genetics
  • Exoribonucleases* / metabolism
  • Models, Theoretical
  • Poly A
  • RNA Stability
  • RNA, Messenger / genetics

Substances

  • RNA, Messenger
  • Exoribonucleases
  • Exonucleases
  • Poly A