Yigong Shi’s Group Reports Molecular Mechanism of RNA Recognition by Lsm2-8 Protein Complex in Nature
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Prof. Yigong Shi’s laboratory in School of Life Sciences, Tsinghua University, reported two crystal structures of Lsm2-8 complex, with or without U6 snRNA 3’ end fragment, which revealed the molecular mechanism of RNA recognition by the pre-assemble protein complex. The paper entitled “Crystal structures of the Lsm complex bound to the 3’ end sequence of U6 small nuclear RNA” was published in Nature online on November 17, 2013.
Precursor messenger RNA (pre-mRNA) undergoes a maturation process where noncoding sequences are removed by splicing in eukaryotic cells. Splicing of pre-mRNA is carried out by the multi-component spliceosome, with more than 100 protein and RNA factors involved. The major components of spliceosome are five small nuclear ribonucleoproteins (snRNPs) known as U1, U2, U4, U5, and U6, each containing a ring-shaped subcomplex of seven proteins and a specific RNA molecule. The heptamer ring in the U6 snRNP comprises seven Lsm proteins: Lsm2-8.
Shi’s team successfully co-expressed all seven Lsm proteins and solved the crystal structures of the Lsm complex with and without RNA fragment. The structure of the RNA-free Lsm2-8 heptamer elucidates the molecular mechanism for the RNA-independent assembly of the heptameric Lsm complex, while the structure of the Lsm2-8 heptamer bound to the U6 snRNA 3’-end fragment reveals a unique mode of RNA recognition – end recognition. The structural investigations, together with the biochemical characterization, serve as an important framework for mechanistic understanding of the U6 snRNP function in pre-mRNA splicing.
This work was supported by funds from National Natural Science Foundation of China projects 31130002 and 31021002. Lijun Zhou, Ph.D. from School of Life Sciences, and Jing Hang, Ph.D. student from School of Medicine are co-first authors. Shanghai Synchrotron Radiation Facility (SSRF) and Spring-8 provided supports for data collection.
The paper link: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12803.html
