ArticlePLoS genetics2013
A novel intra-U1 snRNP cross-regulation mechanism: alternative splicing switch links U1C and U1-70K expression.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Splicing Factors in Plant Abiotic Stress Responses: Regulatory Mechanisms and Perspectives.Plants (Basel, Switzerland) · 2026Review
- An ultraconserved pseudo 5' splice site fine-tunes development by regulating alternative splicing within TOR-related pathways.Nature communications · 2026Article
- Mechanism of alternative splicing of yeast HEH1 through competing 5' splice sites.Nature communications · 2025Article
- A sequential binding mechanism for 5' splice site recognition and modulation for the human U1 snRNP.Nature communications · 2024Article
- The Arabidopsis U1 snRNP regulates mRNA 3'-end processing.Nature plants · 2024Article
- Evolution and stress response potential of the plant splicing factor U1C.Scientific reports · 2024Article
- ZFC3H1 and U1-70K promote the nuclear retention of mRNAs with 5' splice site motifs within nuclear speckles.RNA (New York, N.Y.) · 2022Article
- U1 snRNP telescripting: molecular mechanisms and beyond.RNA biology · 2021Review
- The upstream 5' splice site remains associated to the transcription machinery during intron synthesis.Nature communications · 2021Article
- Biology of the mRNA Splicing Machinery and Its Dysregulation in Cancer Providing Therapeutic Opportunities.International journal of molecular sciences · 2021Review
- Effects of U1 Small Nuclear Ribonucleoprotein Inhibition on the Expression of Genes Involved in Alzheimer's Disease.ACS omega · 2020Article
- Characterizing the interplay between gene nucleotide composition bias and splicing.Genome biology · 2019Article
- The pre-mRNA splicing and transcription factor Tat-SF1 is a functional partner of the spliceosome SF3b1 subunit via a U2AF homology motif interface.The Journal of biological chemistry · 2019Article
- Auto- and cross-regulation of the hnRNPs D and DL.RNA (New York, N.Y.) · 2018Article
- Evidence that C9ORF72 Dipeptide Repeat Proteins Associate with U2 snRNP to Cause Mis-splicing in ALS/FTD Patients.Cell reports · 2017Article
- Alternative exon definition events control the choice between nuclear retention and cytoplasmic export of U11/U12-65K mRNA.PLoS genetics · 2017Article
- The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators.Nucleic acids research · 2016Article
- Therapeutic activity of modified U1 core spliceosomal particles.Nature communications · 2016Article
- Selection preserves Ubiquitin Specific Protease 4 alternative exon skipping in therian mammals.Scientific reports · 2016Article
- The spliceosome assembly factor GEMIN2 attenuates the effects of temperature on alternative splicing and circadian rhythms.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The U1 small nuclear ribonucleoprotein (snRNP)-specific U1C protein participates in 5' splice site recognition and regulation of pre-mRNA splicing. Based on an RNA-Seq analysis in HeLa cells after U1C knockdown, we found a conserved, intra-U1 snRNP cross-regulation that links U1C and U1-70K expression through alternative splicing and U1 snRNP assembly. To investigate the underlying regulatory mechanism, we combined mutational minigene analysis, in vivo splice-site blocking by antisense morpholinos, and in vitro binding experiments. Alternative splicing of U1-70K pre-mRNA creates the normal (exons 7-8) and a non-productive mRNA isoform, whose balance is determined by U1C protein levels. The non-productive isoform is generated through a U1C-dependent alternative 3' splice site, which requires an adjacent cluster of regulatory 5' splice sites and binding of intact U1 snRNPs. As a result of nonsense-mediated decay (NMD) of the non-productive isoform, U1-70K mRNA and protein levels are down-regulated, and U1C incorporation into the U1 snRNP is impaired. U1-70K/U1C-deficient particles are assembled, shifting the alternative splicing balance back towards productive U1-70K splicing, and restoring assembly of intact U1 snRNPs. Taken together, we established a novel feedback regulation that controls U1-70K/U1C homeostasis and ensures correct U1 snRNP assembly and function.
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