Abstract
Pre-mRNA splicing is an essential mechanism for ensuring integrity of the transcriptome in eukaryotes. Therefore, splicing deficiency might cause a decrease in functional proteins and the production of nonfunctional, aberrant proteins. To prevent the production of such aberrant proteins, eukaryotic cells have several mRNA quality control mechanisms. In addition to the known mechanisms, we previously found that transcription elongation is attenuated to prevent the accumulation of pre-mRNA under splicing-deficient conditions. However, the detailed molecular mechanism behind the defect in transcription elongation remains unknown. Here, we showed that the RNA binding protein Rbm38 reduced the transcription elongation defect of the SMEK2 gene caused by splicing deficiency. This reduction was shown to require the N- and C-terminal regions of Rbm38, along with an important role being played by the RNA-recognition motif of Rbm38. These findings advance our understanding of the molecular mechanism of the transcription elongation defect caused by splicing deficiency.
Highlights
Pre-mRNA splicing is an indispensable mechanism for ensuring accurate gene expression in eukaryotes [1,2,3]
To obtain insight into the molecular mechanism of the transcription elongation defect caused by splicing deficiency, we searched for RNA binding proteins (RBPs) that suppress the transcription elongation defect using our RBP library (Table S1)
Following transfection with RBP plasmids, the transfected cells were treated with spliceostatin A (SSA), after which the nascent mRNAs were analysed to measure the expression level of SMEK2 and CDK6 genes, because we previously found that SSA treatment causes a significant transcription elongation defect of these genes [11,12]
Summary
Pre-mRNA splicing is an indispensable mechanism for ensuring accurate gene expression in eukaryotes [1,2,3]. After which the exons are joined by pre-mRNA splicing to produce mature mRNAs. The spliced, mature mRNAs are exported to the cytoplasm and translated into functional proteins. Pre-mRNAs that are exported or leak from the nucleus are degraded by nonsense-mediated mRNA decay (NMD) in the cytoplasm [10]. These mRNA quality control mechanisms prevent the production of aberrant proteins that are translated from pre-mRNAs. In addition to the aforementioned mRNA quality control mechanisms, we found that transcription elongation is attenuated to prevent mRNA accumulation and translation upon treatment with spliceostatin A (SSA), which is a potent splicing inhibitor that binds to
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