Little is known about the spliceosome's structure before its extensive remodeling into a catalytically active complex. Here, we report a 3D cryo-EM structure of a pre-catalytic human spliceosomal B complex. The U2 snRNP-containing head domain is connected to the B complex main body via three main bridges. U4/U6.U5 tri-snRNP proteins, which are located in the main body, undergo significant rearrangements during tri-snRNP integration into the B complex. These include formation of a partially closed Prp8 conformation that creates, together with Dim1, a 5' splice site (ss) binding pocket, displacement of Sad1, and rearrangement of Brr2 such that it contacts its U4/U6 substrate and is poised for the subsequent spliceosome activation step. The molecular organization of several B-specific proteins suggests that they are involved in negatively regulating Brr2, positioning the U6/5'ss helix, and stabilizing the B complex structure. Our results indicate significant differences between the early activation phase of human and yeast spliceosomes.

• PMID: 28781166
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Reference Type

Journal Article

Authors

Bertram K, Agafonov DE, Dybkov O, Haselbach D, Leelaram MN, Will CL, Urlaub H, Kastner B, Lührmann R, Stark H

Primary Lit For

U4/U6.U5 tri-small nuclear ribonucleoprotein complex | U2 small nuclear ribonucleoprotein complex

Additional Lit For

SNR14 | SNU114 | MAK31 | SMX2 | SMD1 | PRP38 | SNU23 | SNR6 | SPP381 | PRP31 | LIN1 | ... Show allPRP8 | PRP18 | LSM8 | BRR2 | SNR7-L | SNR7-S | SMB1 | SNU13 | LSM2 | PRP6 | LSM6 | SMD2 | PRP4 | SMX3 | LSM4 | PRP3 | LSM5 | DIM1 | SME1 | DIB1 | LSM7 | LSM3 | SNU66 | SMD3 Show fewer

Review For