Related Experiment Video

Updated: Jun 23, 2025

Author Spotlight: Exploring the Frontier of mRNA Research with Poly A Tail Analysis Techniques
08:16

Author Spotlight: Exploring the Frontier of mRNA Research with Poly A Tail Analysis Techniques

Published on: January 12, 2024

932

Decoupled degradation and translation enables noise modulation by poly(A) tails

Carmen Grandi1, Martin Emmaneel1, Frank H T Nelissen1

  • 1Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, the Netherlands; Oncode Institute, Nijmegen, the Netherlands.

Cell Systems
|June 20, 2024
PubMed

Insights

Poly(A) tail length regulates mRNA degradation but not translation directly. Optimal tail length enhances translation, offering insights into gene expression and nucleic acid therapeutics.

Area of Science:

  • Molecular Biology
  • Gene Expression Regulation
  • mRNA Metabolism

Background:

  • Polyadenylation is critical for mRNA stability and translation.
  • The precise relationship between poly(A) tail length and mRNA kinetics is not fully understood.

Purpose of the Study:

  • To investigate how poly(A) tail length influences mRNA degradation and translation rates.
  • To determine the impact of poly(A) tail length variability on gene expression.

Main Methods:

  • Utilized a library of identical mRNAs with varying poly(A) tail lengths in human embryonic kidney cells.
  • Employed nanopore sequencing to measure endogenous poly(A) tail lengths.
  • Integrated stochastic modeling with single-cell tracking.

Main Results:

  • Poly(A) tail length strongly correlates with mRNA degradation rates.
  • Translation efficiency is optimized at a poly(A) tail length of approximately 100 nucleotides, matching endogenous levels.
  • Poly(A) tail length variability affects translation efficiency but not degradation rates.

Conclusions:

  • Poly(A) tails serve as a regulatory mechanism to modulate gene expression fluctuations by uncoupling mRNA degradation and translation.
  • Findings enhance the fundamental understanding of gene expression and have implications for nucleic acid therapeutics.
Keywords:
gene expression kineticsmRNA degradation and translationpoly(A)-tail lengthprotein fluctuationsstochastic noise

More Related Videos

Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling10:00

Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling

Published on: October 28, 2014

28.2K
Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs10:37

Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs

Published on: May 10, 2018

12.5K

Related Concept Videos

mRNA Stability and Gene Expression02:51

mRNA Stability and Gene Expression

The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
5.6K
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
10.6K
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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...
889
Nuclear Export of mRNA02:31

Nuclear Export of mRNA

Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.7K
RNA Stability01:53

RNA Stability

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
33.5K
Termination of Translation01:44

Termination of Translation

The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is the site where the peptide bond is formed - and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through...
25.4K