mRNA quality control goes transcriptional

Area of Science:

• Molecular Biology
• Gene Expression Regulation
• RNA Processing

Background:

• Eukaryotic messenger RNAs (mRNAs) require extensive processing, including 5' capping, splicing, and 3' polyadenylation, to become functional.
• Aberrant, unprocessed mRNAs can harm cells, necessitating robust quality control (QC) mechanisms for their identification and degradation.
• Nucleases like Xrn2/Rat1 and the nuclear exosome are key players in the turnover of aberrant mRNAs.

Purpose of the Study:

• To review the mechanisms by which cells co-transcriptionally initiate RNA removal.
• To discuss how cells down-regulate transcription of repeatedly misprocessed transcripts.
• To highlight the integration of mRNA processing QC with transcription.

Main Methods:

• This review synthesizes current research on mRNA quality control.
• It focuses on the interplay between transcription and RNA processing.
• Mechanisms of aberrant RNA turnover and transcriptional regulation are discussed.

Main Results:

• Quality control (QC) acts at the transcriptional level, not just post-transcriptionally.
• Cells can initiate RNA removal during transcription.
• Transcription of faulty transcripts can be actively suppressed.

Conclusions:

• mRNA processing fidelity is monitored co-transcriptionally by quality control mechanisms.
• These mechanisms couple RNA processing with RNA polymerase II (polII) transcription.
• Cells employ strategies to remove aberrant RNAs and down-regulate transcription of persistently erroneous transcripts.