ArticleMolecular and cellular biology2011
FLASH is required for the endonucleolytic cleavage of histone pre-mRNAs but is dispensable for the 5' exonucleolytic degradation of the downstream cleavage product.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 38 citations in OpenAlex.
- Are components of the histone gene expression machinery functionally repurposed in terminally differentiated cells?Biology open · 2026Article
- SUMO2 promotes histone pre-mRNA processing by stabilizing histone locus body interactions and facilitating U7 snRNP assembly.Genes & development · 2025Article
- Proteins that recognize unique features of U7 snRNA and may substitute for Gemin5 in the assembly of U7-specific Sm ring.RNA (New York, N.Y.) · 2025Article
- Anticancer benzoxaboroles block pre-mRNA processing by directly inhibiting CPSF3.Cell chemical biology · 2024Article
- U7 deciphered: the mechanism that forms the unusual 3' end of metazoan replication-dependent histone mRNAs.Biochemical Society transactions · 2021Review
- A real-time fluorescence assay for CPSF73, the nuclease for pre-mRNA 3'-end processing.RNA (New York, N.Y.) · 2021Article
- Replication-dependent histone biosynthesis is coupled to cell-cycle commitment.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A region of SLBP outside the mRNA-processing domain is essential for deposition of histone mRNA into theJournal of cell science · 2021Article
- Reconstitution and biochemical assays of an active human histone pre-mRNA 3'-end processing machinery.Methods in enzymology · 2021Article
- Studies with recombinant U7 snRNP demonstrate that CPSF73 is both an endonuclease and a 5'-3' exonuclease.RNA (New York, N.Y.) · 2020Article
- Recent molecular insights into canonical pre-mRNA 3'-end processing.Transcription · 2020Review
- Composition and processing activity of a semi-recombinant holo U7 snRNP.Nucleic acids research · 2020Article
- Structure of an active human histone pre-mRNA 3'-end processing machinery.Science (New York, N.Y.) · 2020Article
- Positive cofactor 4 (PC4) contributes to the regulation of replication-dependent canonical histone gene expression.BMC molecular biology · 2018Article
- Protein composition of catalytically active U7-dependent processing complexes assembled on histone pre-mRNA containing biotin and a photo-cleavable linker.Nucleic acids research · 2018Article
- Birth and Death of Histone mRNAs.Trends in genetics : TIG · 2017Review
- U7 snRNP is recruited to histone pre-mRNA in a FLASH-dependent manner by two separate regions of the stem-loop binding protein.RNA (New York, N.Y.) · 2017Article
- The N-terminal domains of FLASH and Lsm11 form a 2:1 heterotrimer for histone pre-mRNA 3'-end processing.PloS one · 2017Article
- Mapping the Interaction Network of Key Proteins Involved in Histone mRNA Generation: A Hydrogen/Deuterium Exchange Study.Journal of molecular biology · 2016Article
- FUS/TLS contributes to replication-dependent histone gene expression by interaction with U7 snRNPs and histone-specific transcription factors.Nucleic acids research · 2015Article
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7 authors at 1 institution in 1 country.
Funding
Abstract
3'-end cleavage of histone pre-mRNAs is catalyzed by CPSF-73 and requires the interaction of two U7 snRNP-associated proteins, FLASH and Lsm11. Here, by using scanning mutagenesis we identify critical residues in human FLASH and Lsm11 that are involved in the interaction between these two proteins. We also demonstrate that mutations in the region of FLASH located between amino acids 50 and 99 do not affect binding of Lsm11. Interestingly, these mutations convert FLASH into an inhibitory protein that reduces in vitro processing efficiency of highly active nuclear extracts. Our results suggest that this region in FLASH in conjunction with Lsm11 is involved in recruiting a yet-unknown processing factor(s) to histone pre-mRNA. Following endonucleolytic cleavage of histone pre-mRNA, the downstream cleavage product (DCP) is degraded by the 5'-3' exonuclease activity of CPSF-73, which also depends on Lsm11. Strikingly, while cleavage of histone pre-mRNA is stimulated by FLASH and inhibited by both dominant negative mutants of FLASH and anti-FLASH antibodies, the 5'-3' degradation of the DCP is not affected. Thus, the recruitment of FLASH to the processing complex plays a critical role in activating the endonuclease mode of CPSF-73 but is dispensable for its 5'-3' exonuclease activity. These results suggest that CPSF-73, the catalytic component in both reactions, can be recruited to histone pre-mRNA largely in a manner independent of FLASH, possibly by a separate domain in Lsm11.
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