Roles of mRNA poly(A) tails in regulation of eukaryotic gene expression

Lori A Passmore1, Jeff Coller2

  • 1MRC Laboratory of Molecular Biology, Cambridge, UK. passmore@mrc-lmb.cam.ac.uk.

Insights

Poly(A) tails and poly(A)-binding protein (PABPC) have complex roles in gene regulation, influencing mRNA translation and decay. Recent findings reveal their intricate interplay with deadenylation and translation elongation.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Biochemistry

Background:

  • Polyadenylation is a crucial post-transcriptional modification in eukaryotes, affecting mRNA fate.
  • The cytoplasmic polyadenylate-binding protein (PABPC) is known to interact with poly(A) tails.
  • Previous understanding suggested PABPC and poly(A) tails primarily stabilize mRNA and promote translation.

Purpose of the Study:

  • To review recent advancements in understanding the cytoplasmic functions of poly(A) tails.
  • To elucidate the complex roles of poly(A) tails and PABPC in mRNA translation and stability.
  • To discuss the mechanisms and regulation of deadenylation.

Main Methods:

  • Literature review of recent research on poly(A) tail function.
  • Analysis of experimental data on mRNA decay and translation.
  • Discussion of enzymatic pathways involved in deadenylation.

Main Results:

  • Poly(A) tails and PABPC exhibit more complex roles than previously thought.
  • PABPC can stimulate poly(A) tail removal (deadenylation).
  • Translation elongation rate influences deadenylation, impacting mRNA stability and gene expression.

Conclusions:

  • The interplay between poly(A) tails, PABPC, translation, and mRNA decay is central to gene regulation.
  • Deadenylation, mediated by complexes like CCR4-NOT and PAN2-PAN3, is a key regulatory process.
  • Future research will further unravel the dynamic roles of poly(A) tails in cellular processes.

Related Concept Videos

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...
1.1K
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
23.8K
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
5.9K
Pre-mRNA Processing: Modification of pre-mRNA Ends01:35

Pre-mRNA Processing: Modification of pre-mRNA Ends

In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps...
11.0K
pre-mRNA Processing02:01

pre-mRNA Processing

In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl...
54.3K
What is Gene Expression?01:36

What is Gene Expression?

A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised  of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then...
9.6K