Liang Tong Lab at Columbia University

The Histone pre-mRNA 3'-end Processing Project

Updated Jan. 2020

Metazoan replication-dependent histone pre-mRNAs are cleaved but not polyadenylated at their 3' end. The cleavage site is located between the conserved stem-loop structure and a purine-rich histone downstream element (HDE). The stem-loop is recognized by stem-loop binding protein (SLBP), and 3'-5' exoribonuclease 3'hExo after the cleavage. The HDE base pairs with the 5' region of the U7 snRNA, and the U7 snRNP is critical for histone pre-mRNA processing.

The Sm ring of U7 snRNP contains two unique subunits, Lsm10 and Lsm11, in place of SmD1 and SmD2 of the spliceosomal snRNPs. Lsm11 has a 150 residue long N-terminal extension, and is crucial for interacting FLASH, which in turn recruits the histone pre-mRNA cleavage complex (HCC). Lsm10 has small extensions at its N- and C-termini, but it is not known whether they have any functions.

The HCC contains CPSF73, CPSF100, symplekin and CstF64, with CPSF73 being the endonuclease that catalyzes the cleavage reaction. The HCC is equivalent to the mammalian cleavage factor (mCF) in the canonical processing machinery, with CPSF73 as the endonuclease in both machineries.

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