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The N-terminal domains of FLASH and Lsm11 form a 2:1 heterotrimer for histone pre-mRNA 3'-end processing.

ABSTRACT: Unlike canonical pre-mRNAs, animal replication-dependent histone pre-mRNAs lack introns and are processed at the 3'-end by a mechanism distinct from cleavage and polyadenylation. They have a 3' stem loop and histone downstream element (HDE) that are recognized by stem-loop binding protein (SLBP) and U7 snRNP, respectively. The N-terminal domain (NTD) of Lsm11, a component of U7 snRNP, interacts with FLASH NTD and these two proteins recruit the histone cleavage complex containing the CPSF-73 endonuclease for the cleavage reaction. Here, we determined crystal structures of FLASH NTD and found that it forms a coiled-coil dimer. Using solution light scattering, we characterized the stoichiometry of the FLASH NTD-Lsm11 NTD complex and found that it is a 2:1 heterotrimer, which is supported by observations from analytical ultracentrifugation and crosslinking.

SUBMITTER: Aik WS

PROVIDER: S-EPMC5636114 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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The N-terminal domains of FLASH and Lsm11 form a 2:1 heterotrimer for histone pre-mRNA 3'-end processing.

Aik Wei Shen WS Lin Min-Han MH Tan Dazhi D Tripathy Ashutosh A Marzluff William F WF Dominski Zbigniew Z Chou Chi-Yuan CY Tong Liang L

PloS one 20171011 10

Unlike canonical pre-mRNAs, animal replication-dependent histone pre-mRNAs lack introns and are processed at the 3'-end by a mechanism distinct from cleavage and polyadenylation. They have a 3' stem loop and histone downstream element (HDE) that are recognized by stem-loop binding protein (SLBP) and U7 snRNP, respectively. The N-terminal domain (NTD) of Lsm11, a component of U7 snRNP, interacts with FLASH NTD and these two proteins recruit the histone cleavage complex containing the CPSF-73 endo ...[more]

PMID: 29020104

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