Metazoan oocyte and early embryo development program: a progression through translation regulatory cascades.
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Animals↗
Biomedical subjects
Shobha Vasudevan
Publications and source records attributed to Shobha Vasudevan.
p38 mitogen-activated protein kinase/Hog1p regulates translation of the AU-rich-element-bearing MFA2 transcript.
AU-rich-element (ARE)-mediated mRNA regulation occurs in Saccharomyces cerevisiae in response to external and internal stimuli through the p38 mitogen-activated protein kinase (MAPK)/Hog1p pathway. We demonstrate that the ARE-bearing MFA2 3' untranslated region (UTR) controls translation efficiency in a p38 MAPK/Hog1p-dependent manner in response to carbon source growth conditions. The carbon source-regulated effect on MFA2 3'-UTR-controlled translation involves the role of conserved ARE binding proteins, the ELAV/TIA-1-like Pub1p, which can interact with the cap/eIF4G complex, and the translation/mRNA stability factor poly(A) binding protein (Pab1p). Pub1p binds the MFA2 3'-UTR in a p38 MAPK/Hog1p-regulated manner in response to carbon source growth conditions. Significantly, the p38 MAPK/Hog1p is also required to modulate Pab1p in response to carbon source. We find that Pab1p can bind the MFA2 3'-UTR in a regulated manner to control MFA2 3'-UTR reporter translation. Binding of full-length Pab1p to the MFA2 3'-UTR correlates with translation repression. Importantly, Pab1p binds the MFA2 3'-UTR only in a PUB1 strain, and correlating with this requirement, Pub1p controls translation repression of MFA2 in a carbon source/Hog1p-regulated manner. These results suggest that the p38 MAPK/Hog1p pathway regulates 3'-UTR-mediated translation by modulating recruitment of Pab1p and Pub1p, which can interact with the translation machinery.
3' Untranslated Regions↗
Nuclear mRNA surveillance.
Recent studies demonstrate that the factors involved in mRNA processing specify the fate of a transcript. The mRNA is either committed for export to the cytoplasm or accumulates in the nucleus, where it may be degraded. These studies reveal crosstalk among the nuclear events faced by the pre-mRNA. It is becoming evident that the components of the mRNA synthesis machinery interact with each other to establish a distinct surveillance mechanism that determines release of the transcript from the transcription site for further export and utilisation. Recent advances suggest that the major nuclear decay machinery, the nuclear exosome, and an Rrp6p-specific complex coordinate with processing factors to perform a unique regulatory function that determines its fate: either confinement of the defective mRNA at its transcription site, or release from its site of transcription for further processing and export or decay. Furthermore, message-specific regulatory mechanisms correspond with the nuclear mRNA synthesis machinery to control gene expression.
Animals↗
A yeast homologue of Hsp70, Ssa1p, regulates turnover of the MFA2 transcript through its AU-rich 3' untranslated region.
Many eukaryotic mRNAs exhibit regulated decay in response to cellular signals. AU-rich elements (AREs) identified in the 3' untranslated region (3'-UTR) of several such mRNAs play a critical role in controlling the half-lives of these transcripts. The yeast ARE-containing mRNA, MFA2, has been studied extensively and is degraded by a deadenylation-dependent mechanism. However, the trans-acting factors that promote the rapid decay of MFA2 have not been identified. Our results suggest that the chaperone protein Hsp70, encoded by the SSA family of genes, is involved in modulating MFA2 mRNA decay. MFA2 is specifically stabilized in a strain bearing a temperature-sensitive mutation in the SSA1 gene. Furthermore, an AU-rich region within the 3'-UTR of the message is both necessary and sufficient to confer this regulation. Stabilization occurs as a result of slower deadenylation in the ssa1(ts) strain, suggesting that Hsp70 is required for activation of the turnover pathway.
3' Untranslated Regions↗
Non-stop decay--a new mRNA surveillance pathway.
Gene expression is an inherently complex process and errors often occur during the transcription and processing of mRNAs. Several surveillance mechanisms have evolved to check the fidelity at each step of mRNA manufacture. Two recent reports describe the identification of a novel pathway in eukaryotes that recognizes and degrades mRNAs that lack a stop codon. The non-stop decay mechanism releases ribosomes stalled at the 3' end of a mRNA and stimulates the exosome to rapidly degrade the transcript.
3' Untranslated Regions↗