An official website of the United States government
Abstract MOV10 is an RNA helicase that associates with the RNA‐induced silencing complex component Argonaute (AGO), likely resolving RNA secondary structures. MOV10 also binds the Fragile X mental retardation protein to block AGO2 binding at some sites and associates with UPF1, a principal component of the nonsense‐mediated RNA decay pathway. MOV10 is widely expressed and has a key role in the cellular response to viral infection and in suppressing retrotransposition. Posttranslational modifications of MOV10 include ubiquitination, which leads to stimulation‐dependent degradation, and phosphorylation, which has an unknown function. MOV10 localizes to the nucleus and/or cytoplasm in a cell type‐specific and developmental stage‐specific manner. Knockout ofMov10leads to embryonic lethality, underscoring an important role in development where it is required for the completion of gastrulation. MOV10 is expressed throughout the organism; however, most studies have focused on germline cells and neurons. In the testes, the knockdown ofMov10disrupts proliferation of spermatogonial progenitor cells. In brain, MOV10 is significantly elevated postnatally and binds mRNAs encoding cytoskeleton and neuron projection proteins, suggesting an important role in neuronal architecture. HeterozygousMov10mutant mice are hyperactive and anxious and their cultured hippocampal neurons have reduced dendritic arborization. Zygotic knockdown ofMov10inXenopus laeviscauses abnormal head and eye development and mislocalization of neuronal precursors in the brain. Thus, MOV10 plays a vital role during development, defense against viral infection and in neuronal development and function: its many roles and regulation are only beginning to be unraveled. 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 Implications
more »
« less
This content will become publicly available on November 1, 2026
Mixed Messages: Dynamic and Compositional Heterogeneity of Nuclear Messenger Ribonucleoprotein ( mRNP ) Complexes
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
more »
« less
- Award ID(s):
- 2140761
- PAR ID:
- 10656032
- Publisher / Repository:
- Wiley
- Date Published:
- Journal Name:
- WIREs RNA
- Volume:
- 16
- Issue:
- 6
- ISSN:
- 1757-7004
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
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.more » « less
-
Controlled by disorder: Phosphorylation modulates SRSF1 domain availability for spliceosome assemblyAbstract Serine/arginine‐rich splicing factor 1 (SRSF1) is key in the mRNA lifecycle including transcription, splicing, nonsense‐mediated decay, and nuclear export. Consequently, its dysfunction is linked to cancers, viral evasion, and developmental disorders. The functionality of SRSF1 relies on its interactions with other proteins and RNA molecules. These processes are regulated by phosphorylation of its unstructured arginine/serine‐rich tail (RS). Here, we characterize how phosphorylation affects SRSF1's protein and RNA interaction and phase separation. Using NMR paramagnetic relaxation enhancement and chemical shift perturbation, we find that when unphosphorylated, SRSF1's RS interacts with its first RNA‐recognition motif (RRM1). Phosphorylation of RS decreases its interactions with the protein‐binding site of RRM1 and increases its interactions with the RNA‐binding site of RRM1. This change in SRSF1's intramolecular interactions increases the availability of protein‐interacting sites on RRM1 and weakens RNA binding of SRSF1. Phosphorylation alters the phase separation of SRSF1 by diminishing the role of arginine in intermolecular interactions. These findings provide an unprecedented view of how SRSF1 influences the early‐stage spliceosome assembly.more » « less
-
Summary A network of peptidases governs proteostasis in plant chloroplasts and mitochondria. This study reveals strong genetic and functional interactions in Arabidopsis between the chloroplast stromal CLP chaperone‐protease system and the PREP1,2 peptidases, which are dually localized to chloroplast stroma and the mitochondrial matrix.Higher order mutants defective in CLP or PREP proteins were generated and analyzed by quantitative proteomics and N‐terminal proteomics (terminal amine isotopic labeling of substrates (TAILS)).Strong synergistic interactions were observed between the CLP protease system (clpr1‐2,clpr2‐1,clpc1‐1,clpt1,clpt2)and both PREP homologs (prep1,prep2) resulting in embryo lethality or growth and developmental phenotypes. Synergistic interactions were observed even when only one of the PREP proteins was lacking, suggesting that PREP1 and PREP2 have divergent substrates. Proteome phenotypes were driven by the loss of CLP protease capacity, with little impact from the PREP peptidases. Chloroplast N‐terminal proteomesshowed that many nuclear encoded chloroplast proteins have alternatively processed N‐termini inprep1prep2,clpt1clpt2andprep1prep2clpt1clpt2.Loss of chloroplast protease capacity interferes with stromal processing peptidase (SPP) activity due to folding stress and low levels of accumulated cleaved cTP fragments. PREP1,2 proteolysis of cleaved cTPs is complemented by unknown proteases. A model for CLP and PREP activity within a hierarchical chloroplast proteolysis network is proposed.more » « less
-
Summary Nuclear speckles are membraneless organelles implicated in multiple RNA processing steps. In this work, we systematically characterize the sequence logic determining RNA localization to nuclear speckles. We find extensive similarities between the speckle localization code and the RNA splicing code, even for transcripts that do not undergo splicing. Specifically, speckle localization is enhanced by the presence of unspliced exon-like or intron-like sequence features. We demonstrate that interactions required for early splicesomal complex assembly contribute to speckle localization. We also show that speckle localization of isolated endogenous exons is reduced by disease-associated single nucleotide variants. Finally, we find that speckle localization strongly correlates with splicing kinetics of splicing-competent constructs and is tightly linked to the decision between exon inclusion and skipping. Together, these results suggest a model in which RNA speckle localization is associated with the formation of the early spliceosomal complex and enhances the efficiency of splicing reactions. HighlightsSequences containing hallmarks of pre-mRNA dictate speckle localizationRNA speckle localization is coupled to early spliceosome assemblyDisease-associated single nucleotide variants reduce localization of isolated exonsRNA speckle localization strongly correlates with splicing kineticsGraphical Abstractmore » « less
