Molecular impact of mutations in RNA splicing factors in cancer
Q Zhang, Y Ai, O Abdel-Wahab - Molecular Cell, 2024 - cell.com
Somatic mutations in genes encoding components of the RNA splicing machinery occur
frequently in multiple forms of cancer. The most frequently mutated RNA splicing factors in …
frequently in multiple forms of cancer. The most frequently mutated RNA splicing factors in …
Pre-mRNA splicing-associated diseases and therapies
Precursor mRNA (pre-mRNA) splicing is an essential step in human gene expression and is
carried out by a large macromolecular machine called the spliceosome. Given the …
carried out by a large macromolecular machine called the spliceosome. Given the …
GPATCH8 modulates mutant SF3B1 mis-splicing and pathogenicity in hematologic malignancies
Mutations in the RNA splicing factor gene SF3B1 are common across hematologic and solid
cancers and result in widespread alterations in splicing, yet there is currently no therapeutic …
cancers and result in widespread alterations in splicing, yet there is currently no therapeutic …
The splicing regulators RBM5 and RBM10 are subunits of the U2 snRNP engaged with intron branch sites on chromatin
A Damianov, CH Lin, J Huang, L Zhou… - Molecular Cell, 2024 - cell.com
Understanding the mechanisms of pre-mRNA splicing is limited by the technical challenges
to examining spliceosomes in vivo. Here, we report the isolation of RNP complexes derived …
to examining spliceosomes in vivo. Here, we report the isolation of RNP complexes derived …
Mechanism for the initiation of spliceosome disassembly
MK Vorländer, P Rothe, J Kleifeld, ED Cormack… - Nature, 2024 - nature.com
Abstract Precursor-mRNA (pre-mRNA) splicing requires the assembly, remodelling and
disassembly of the multi-megadalton ribonucleoprotein complex called the spliceosome …
disassembly of the multi-megadalton ribonucleoprotein complex called the spliceosome …
Characterization of the SF3B1–SUGP1 interface reveals how numerous cancer mutations cause mRNA missplicing
The spliceosomal gene SF3B1 is frequently mutated in cancer. While it is known that SF3B1
hotspot mutations lead to loss of splicing factor SUGP1 from spliceosomes, the cancer …
hotspot mutations lead to loss of splicing factor SUGP1 from spliceosomes, the cancer …
Targeted high-throughput mutagenesis of the human spliceosome reveals its in vivo operating principles
The spliceosome is a staggeringly complex machine, comprising, in humans, 5 snRNAs
and> 150 proteins. We scaled haploid CRISPR-Cas9 base editing to target the entire human …
and> 150 proteins. We scaled haploid CRISPR-Cas9 base editing to target the entire human …
[HTML][HTML] Dynamic interactions drive early spliceosome assembly
Splicing is a critical processing step during pre-mRNA maturation in eukaryotes. The correct
selection of splice sites during the early steps of spliceosome assembly is highly important …
selection of splice sites during the early steps of spliceosome assembly is highly important …
[HTML][HTML] Splicing quality control mediated by DHX15 and its G-patch activator SUGP1
Q Feng, K Krick, J Chu, CB Burge - Cell reports, 2023 - cell.com
Pre-mRNA splicing is surveilled at different stages by quality control (QC) mechanisms. The
leukemia-associated DExH-box family helicase hDHX15/scPrp43 is known to disassemble …
leukemia-associated DExH-box family helicase hDHX15/scPrp43 is known to disassemble …
[HTML][HTML] Structural basis of catalytic activation in human splicing
Pre-mRNA splicing follows a pathway driven by ATP-dependent RNA helicases. A crucial
event of the splicing pathway is the catalytic activation, which takes place at the transition …
event of the splicing pathway is the catalytic activation, which takes place at the transition …