Modulating splicing with small molecular inhibitors of the spliceosome

KA Effenberger, VK Urabe… - Wiley Interdisciplinary …, 2017 - Wiley Online Library
Small molecule inhibitors that target components of the spliceosome have great potential as
tools to probe splicing mechanism and dissect splicing regulatory networks in cells. These …

RNA helicases in splicing

O Cordin, JD Beggs - RNA biology, 2013 - Taylor & Francis
In eukaryotic cells, introns are spliced from pre-mRNAs by the spliceosome. Both the
composition and the structure of the spliceosome are highly dynamic, and eight DExD/H …

Cryo-EM structure of a human spliceosome activated for step 2 of splicing

K Bertram, DE Agafonov, WT Liu, O Dybkov, CL Will… - Nature, 2017 - nature.com
Spliceosome rearrangements facilitated by RNA helicase PRP16 before catalytic step two of
splicing are poorly understood. Here we report a 3D cryo-electron microscopy structure of …

Cryo-EM structure of a pre-catalytic human spliceosome primed for activation

K Bertram, DE Agafonov, O Dybkov, D Haselbach… - Cell, 2017 - cell.com
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 …

The architecture of the spliceosomal U4/U6. U5 tri-snRNP

THD Nguyen, WP Galej, X Bai, CG Savva, AJ Newman… - Nature, 2015 - nature.com
Abstract U4/U6. U5 tri-snRNP is a 1.5-megadalton pre-assembled spliceosomal complex
comprising U5 small nuclear RNA (snRNA), extensively base-paired U4/U6 snRNAs and …

Mechanism of 5ʹ splice site transfer for human spliceosome activation

C Charenton, ME Wilkinson, K Nagai - Science, 2019 - science.org
The prespliceosome, comprising U1 and U2 small nuclear ribonucleoproteins (snRNPs)
bound to the precursor messenger RNA 5ʹ splice site (5ʹSS) and branch point sequence …

Molecular architecture of the human U4/U6. U5 tri-snRNP

DE Agafonov, B Kastner, O Dybkov, RV Hofele, WT Liu… - Science, 2016 - science.org
The U4/U6. U5 triple small nuclear ribonucleoprotein (tri-snRNP) is a major spliceosome
building block. We obtained a three-dimensional structure of the 1.8-megadalton human tri …

Mechanism of protein-guided folding of the active site U2/U6 RNA during spliceosome activation

C Townsend, MN Leelaram, DE Agafonov, O Dybkov… - Science, 2020 - science.org
INTRODUCTION The spliceosome, including its catalytic center, is formed anew on each pre-
mRNA intron, through a pathway involving multiple, successive assembly intermediates …

Molecular architecture of the human 17S U2 snRNP

Z Zhang, CL Will, K Bertram, O Dybkov, K Hartmuth… - Nature, 2020 - nature.com
The U2 small nuclear ribonucleoprotein (snRNP) has an essential role in the selection of the
precursor mRNA branch-site adenosine, the nucleophile for the first step of splicing. Stable …

A human postcatalytic spliceosome structure reveals essential roles of metazoan factors for exon ligation

SM Fica, C Oubridge, ME Wilkinson, AJ Newman… - Science, 2019 - science.org
During exon ligation, the Saccharomyces cerevisiae spliceosome recognizes the 3′-splice
site (3′ SS) of precursor messenger RNA (pre-mRNA) through non–Watson-Crick pairing …