Degradation of YRA1 Pre-mRNA in the cytoplasm requires translational repression, multiple modular intronic elements,

Shuyun Dong1, Allan Jacobson, Feng He

  • 1Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.

Plos Biology
|May 14, 2010
PubMed

Insights

Yeast YRA1 pre-mRNA uses a unique cytoplasmic decay pathway involving Edc3p, independent of translation. This process involves specific intronic elements for Edc3p targeting and translational repression, preventing nonsense-mediated decay.

Area of Science:

  • Molecular Biology
  • RNA Metabolism
  • Gene Regulation

Background:

  • Intron-containing pre-mRNAs are typically nuclear-processed but can be exported to the cytoplasm.
  • Nonsense-mediated mRNA decay (NMD) degrades cytoplasmic pre-mRNAs with premature termination codons.
  • Yeast YRA1 pre-mRNA evades NMD through autoregulated nuclear export, engaging a distinct cytoplasmic decay pathway.

Purpose of the Study:

  • To elucidate the transcript-specific cytoplasmic decay mechanism of yeast YRA1 pre-mRNA.
  • To identify the roles of Edc3p and intronic elements in YRA1 pre-mRNA degradation.
  • To understand the interplay between translational repression and NMD evasion in YRA1 pre-mRNA regulation.

Main Methods:

  • Investigated Edc3p-mediated degradation of YRA1 pre-mRNA.
  • Analyzed the function of five modular elements within the YRA1 intron.
  • Examined the role of the Mex67p/Mtr2p export receptor in translational repression and NMD susceptibility.

Main Results:

  • YRA1 pre-mRNA degradation by Edc3p is translation-independent.
  • Five intronic elements control Edc3p substrate targeting and translational repression.
  • Mex67p/Mtr2p mediates translational repression, enhancing Edc3p specificity by inhibiting NMD.

Conclusions:

  • YRA1 pre-mRNA degradation is a regulated process involving translational repression and Edc3p-mediated decapping.
  • Specific intronic elements dictate substrate recognition and translational control.
  • The pathway ensures efficient degradation while preventing premature NMD, highlighting complex RNA regulation.

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
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
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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...
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...
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 addition of a...