研究セミナー Structural studies of the spliceosome by cryo-electron microscopy

Introns are removed from pre-messenger RNA by a large, dynamic molecular machine called the spliceosome. The spliceosome assembles on pre-mRNA by the ordered joining of five small ribonucleoprotein particles (U1, U2, U4/U6 and U5 snRNPs) and numerous proteins, including the large nineteen and nineteen-related complexes (NTC and NTR). The U1 and U2 snRNPs initially recognise the 5'-splice site and branch site of the pre-mRNA, and the U4/U6.U5 tri-snRNP joins to produce a fully assembled but inactive complex. RNA helicases then extensively remodel the spliceosome, resulting in formation of a group II-intron like catalytic core, in which U6 snRNA catalyses two consecutive transesterification reactions. High resolution structural studies of the spliceosome have been hampered by its enormous complexity and highly dynamic nature. Recent developments in cryo-electron microscopy have provided solutions to some of these problems. In this talk I will present my cryo-EM work on the spliceosome and discuss its important biological implications.