Transcription termination promotes splicing efficiency and fidelity in a compact genome
Barr, K.; He, K. L.; Krumbein, A. J.; CHANFREAU, G. F.
Show abstract
Splicing of terminal introns is coupled to 3'-end processing by cleavage and polyadenylation (CPA) of mRNAs in mammalian genes. Whether this functional coupling is universally conserved across eukaryotes is unclear. Here we show using long read RNA sequencing in S.cerevisiae that splicing inactivation does not result in widespread CPA impairment. We also show that inactivation of CPA has limited impact on splicing efficiency. The negative impact of CPA inactivation on splicing is mainly due to transcription termination defects that promote readthrough transcription, leading to splicing inhibition for downstream intron-containing genes. Splicing impairment due to 5' extensions is length-dependent and can be detected independently from CPA inactivation for endogenous or synthetic genes, and is likely due to an increased distance of splicing signals to the 5' cap. Finally, we found that deficient termination can promote novel intragenic and long-range intergenic splicing events. These results argue against a broad coupling between splicing and CPA in S.cerevisiae but show that efficient CPA-mediated transcription termination is critical for splicing fidelity and efficiency in a compact genome. Significance StatementAccurate gene expression requires that the enzyme that polymerizes RNA stops at the proper site (termination). In addition multiple RNA processing reactions, including removal of intervening sequences are necessary to produce mature mRNAs. How these different steps in the RNA biogenesis pathways influence each other is not well understood. In this study, we show that inactivation of termination induces mature RNA formation defects, including long RNAs that retain intervening sequences, or chimeric RNAs containing sequences from genes located next to each other on the genome. This study underscores the importance of proper termination to ensure accurate and efficient splicing of adjacent genes, which is particularly critical for compact genomes in which genes are located close to each other.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Spliceosomal mutations decouple 3' splice site fidelity from cellular fitness 96%
- Exon junction complex-associated multi-adapter RNPS1 nucleates splicing regulatory complexes to maintain transcriptome surveillance 94%
- Distinct functions for the paralogous RBM41 and U11/U12-65K proteins in the minor spliceosome 94%
Similar papers in this journal
- Broad variation in response of individual introns to splicing inhibitors in a humanized yeast strain 95%
- A Budding Yeast Model for Human Disease Mutations in the EXOSC2 Cap Subunit of the RNA Exosome 95%
- Synthesis of modified nucleotide polymers by the poly(U) polymerase Cid1: Application to direct RNA sequencing on nanopores. 94%
Similar papers in this journal
- Altered tRNA processing is linked to a distinct and unusual La protein in Tetrahymena thermophila 94%
- LUC7 proteins define two major classes of 5' splice sites in animals and plants 94%
- Coordination of Alternative Splicing and Alternative Polyadenylation revealed by Targeted Long Read Sequencing 94%
Similar papers in this journal
- Xrn1 influence on gene transcription results from the combination of general effects on elongating RNA pol II and gene-specific chromatin configuration 94%
- Rpb4 and Puf3 imprint and post-transcriptionally control the stability of a common set of mRNAs in yeast 94%
- RNA polymerase II is recruited to DNA double-strand breaks for dilncRNA transcription in Drosophila 93%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.