<i>LARP4</i> mRNA codon-tRNA match contributes to LARP4 activity for ribosomal protein mRNA poly(A) tail length protection.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28895529.
- Also identified by DOI 10.7554/eLife.28889 and PMC identifier 5626478.
- Licence recorded as CC0.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Messenger RNA function is controlled by the 3' poly(A) tail (PAT) and poly(A)-binding protein (PABP). La-related protein-4 (LARP4) binds poly(A) and PABP. <i>LARP4</i> mRNA contains a translation-dependent, coding region determinant (CRD) of instability that limits its expression. Although the CRD comprises <10% of LARP4 codons, the mRNA levels vary >20 fold with synonymous CRD substitutions that accommodate tRNA dynamics. Separately, overexpression of the most limiting tRNA increases LARP4 levels and reveals its functional activity, net lengthening of the PATs of heterologous mRNAs with concomitant stabilization, including ribosomal protein (RP) mRNAs. Genetic deletion of cellular LARP4 decreases PAT length and RPmRNA stability. This LARP4 activity requires its PABP-interaction domain and the RNA-binding module which we show is sensitive to poly(A) 3'-termini, consistent with protection from deadenylation. The results indicate that LARP4 is a posttranscriptional regulator of ribosomal protein production in mammalian cells and suggest that this activity can be controlled by tRNA levels.
Medical subject headings
- Autoantigens
- Gene Expression Regulation
- RNA, Messenger
- RNA, Transfer
- Ribonucleoproteins
- Ribosomal Proteins