TY - JOUR
T1 - The N-terminal domains of FLASH and Lsm11 form a 2:1 heterotrimer for histone pre-mRNA 3’-end processing
AU - Aik, Wei Shen
AU - Lin, Min Han
AU - Tan, Dazhi
AU - Tripathy, Ashutosh
AU - Marzluff, William F.
AU - Dominski, Zbigniew
AU - Chou, Chi Yuan
AU - Tong, Liang
N1 - Funding information:
This research is supported by NIH grants R35GM118093 and S10OD012018 (to LT) and GM29832 (to WFM and ZD) and Taiwan MOST grant 105-2320-B-010-012 and 106-2320-B-010-013 (to CYC). This work is based upon research conducted at the Northeastern Collaborative Access Team beamlines (NIH P41 GM103403), using the Pilatus 6M detector (NIH-ORIP HEI grant S10 RR029205).
Publisher Copyright:
© 2017 Aik et al.
PY - 2017/10/11
Y1 - 2017/10/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85031288992&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0186034
DO - 10.1371/journal.pone.0186034
M3 - Journal article
C2 - 29020104
AN - SCOPUS:85031288992
SN - 1932-6203
VL - 12
JO - PLoS ONE
JF - PLoS ONE
IS - 10
M1 - e0186034
ER -