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ABSTRACT Messenger ribonucleoprotein (mRNP) complexes assemble co‐transcriptionally in the nucleus as RNA‐binding proteins (RBPs) engage nascent transcripts. Ongoing RNA processing and RBP dynamics generate a diverse set of mRNPs, often producing a mature mRNA—capped, spliced, and polyadenylated—within a compact mRNP particle poised for nuclear export. The processing, packaging, and export of nuclear mRNPs are tightly regulated to ensure the fidelity of gene expression and to reprogram cellular function under changing organismal and environmental conditions. Understanding the compositional and organizational dynamics of nuclear mRNP assembly and maturation is essential, as dysregulation is linked to viral infections and a range of human diseases, including neurological disorders and cancer. Recent structural, biochemical, and in‐cell studies have revealed key roles for the evolutionarily conserved Yra1/ALYREF proteins and the TRanscription‐EXport (TREX) complex in mRNP packaging and export, highlighting broadly conserved functions across eukaryotes. While many questions remain, these advances have deepened our understanding of nuclear mRNA metabolism and offer new opportunities to investigate how disruptions in mRNA biogenesis and export factors, and their associated processes, contribute to disease. This article is categorized under:RNA Interactions with Proteins and Other Molecules > RNA‐Protein ComplexesRNA Interactions with Proteins and Other Molecules > Protein‐RNA Interactions: Functional ImplicationsRNA Export and Localization > Nuclear Export/Import
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A time-resolved framework for the recruitment of mRNP processing and assembly factors to a site of transcription
Abstract Processing and packaging of messenger ribonucleoprotein (mRNP) particles involve complex, coordinated interactions between nascent transcripts, RNA-binding proteins (RBPs), and associated factors. Despite the critical role of co-transcriptional mRNP assembly in gene expression, the temporal dynamics of this process are not well understood. Here, a live cell imaging assay is reported in Saccharomyces cerevisiae to detect recruitment of endogenous fluorescently tagged proteins to a transcriptionally active locus. Protein recruitment to an inducible integrated gene array composed of 25 transcriptional units is detected by colocalization with lacO repeats. Using arrays with two different promoters and the same coding sequence (GFA1), arrival times for a variety of mRNP processing and assembly factors were quantified. These analyses revealed Yra1, Cbp80, and Yhs7 as pioneering mRNP assembly factors. Notably, Yra1 recruitment occurs independently of the THO complex, with early localization supported by Cbp80 and the RNA recognition motif of Yra1. Altogether, this work establishes the first comprehensive temporal framework for understanding protein recruitment during co-transcriptional mRNP assembly, providing mechanistic insights into the dependencies of Yra1 recruitment.
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- Award ID(s):
- 2140761
- PAR ID:
- 10628908
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- Nucleic Acids Research
- Volume:
- 53
- Issue:
- 15
- ISSN:
- 0305-1048
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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