CNOT6 regulates a novel pattern of mRNA deadenylation during oocyte meiotic maturation

Karl-Frédéric Vieux1,2, Hugh J Clarke3,4,5

  • 1Department of Biology, McGill University, Montreal, Quebec, Canada.

Scientific Reports
|May 3, 2018
PubMed

Insights

Oocyte maturation involves complex mRNA polyadenylation patterns. A newly identified pattern shows mRNAs are deadenylated, then polyadenylated, and deadenylated again, challenging previous models of mRNA regulation.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Background:

  • mRNA polyadenylation regulates gene expression in all cell types.
  • Mammalian oocyte development exhibits distinct mRNA polyadenylation patterns influencing translation and degradation.
  • Existing models do not fully explain mRNA fate during oocyte maturation.

Purpose of the Study:

  • To identify and characterize novel mRNA polyadenylation patterns during mammalian oocyte maturation.
  • To investigate the role of the deadenylase CNOT6 and PUF-binding elements (PBEs) in regulating mRNA polyadenylation.
  • To determine the functional consequences of a long poly(A) tail in this context.

Main Methods:

  • Analysis of mRNA polyadenylation dynamics during oocyte growth and maturation.
  • Localization studies of the deadenylase CNOT6.
  • Investigation of the role of PUF-binding elements (PBEs) in mRNA regulation.
  • Assessment of mRNA translation and degradation rates.

Main Results:

  • A third mRNA polyadenylation pattern was identified: deadenylation during growth, polyadenylation during early maturation, and deadenylation during late maturation.
  • CNOT6 localizes to cortical foci and regulates deadenylation of specific mRNAs.
  • PBEs are involved in regulating deadenylation in mature oocytes.
  • Maintaining a long poly(A) tail did not enhance translation or inhibit degradation for these specific mRNAs.

Conclusions:

  • Mammalian oocyte maturation involves more complex mRNA polyadenylation regulation than previously understood.
  • CNOT6 and PBEs are key players in the novel mRNA polyadenylation pathway.
  • The functional significance of a long poly(A) tail in this specific oocyte context differs from general cellular mechanisms.

Related Concept Videos

Regulated mRNA Transport02:22

Regulated mRNA Transport

In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
7.0K
Regulated mRNA Transport02:22

Regulated mRNA Transport

3.4K
Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
8.3K
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
6.7K
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...
26.5K
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...
8.8K