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Formation of the 3' end of histone mRNA
1Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill 27599, USA.
Abstract:
All metazoan messenger RNAs, with the exception of the replication-dependent histone mRNAs, terminate at the 3' end with a poly(A) tail. Replication-dependent histone mRNAs end instead in a conserved 26-nucleotide sequence that contains a 16-nucleotide stem-loop. Formation of the 3' end of histone mRNA occurs by endonucleolytic cleavage of pre-mRNA releasing the mature mRNA from the chromatin template. Cleavage requires several trans-acting factors, including a protein, the stem-loop binding protein (SLBP), which binds the 26-nucleotide sequence; and a small nuclear RNP, U7 snRNP. There are probably additional factors also required for cleavage. One of the functions of the SLBP is to stabilize binding of the U7 snRNP to the histone pre-mRNA. In the nucleus, both U7 snRNP and SLBP are present in coiled bodies, structures that are associated with histone genes and may play a direct role in histone pre-mRNA processing in vivo. One of the major regulatory events in the cell cycle is regulation of histone pre-mRNA processing, which is at least partially mediated by cell-cycle regulation of the levels of the SLBP protein.
Insights
Histone messenger RNAs (mRNAs) use a unique stem-loop sequence for 3' end formation, unlike most mRNAs with poly(A) tails. This process involves stem-loop binding protein (SLBP) and U7 small nuclear ribonucleoprotein (snRNP) for efficient processing.
Area of Science:
- Molecular Biology
- RNA Processing
- Gene Regulation
Background:
- Most metazoan messenger RNAs (mRNAs) terminate with a poly(A) tail.
- Replication-dependent histone mRNAs possess a distinct 3' end structure, a conserved 26-nucleotide sequence featuring a 16-nucleotide stem-loop.
Purpose of the Study:
- To elucidate the molecular mechanisms and factors involved in the 3' end processing of replication-dependent histone pre-mRNAs.
- To investigate the roles of stem-loop binding protein (SLBP) and U7 small nuclear ribonucleoprotein (snRNP) in histone mRNA maturation.
Main Methods:
- The study focuses on the biochemical interactions and cellular localization of key proteins involved in histone mRNA 3' end formation.
- Analysis of trans-acting factors, including SLBP and U7 snRNP, essential for endonucleolytic cleavage of histone pre-mRNA.
Main Results:
- Histone mRNA 3' end formation relies on endonucleolytic cleavage of pre-mRNA, not polyadenylation.
- Stem-loop binding protein (SLBP) binds the conserved stem-loop sequence and stabilizes U7 snRNP binding to histone pre-mRNA.
- SLBP and U7 snRNP are localized in nuclear coiled bodies, which are associated with histone genes and implicated in pre-mRNA processing.
Conclusions:
- The 3' end processing of histone mRNAs is a complex mechanism involving SLBP and U7 snRNP, distinct from the canonical polyadenylation pathway.
- Cell-cycle regulation of SLBP protein levels plays a significant role in controlling histone mRNA processing, a key regulatory event during the cell cycle.