A5056271884- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- Bacterial Genetics and Biotechnology
- Enzyme Structure and Function
- Fungal and yeast genetics research
- Bacteriophages and microbial interactions
- RNA Interference and Gene Delivery
- RNA regulation and disease
- Nuclear Structure and Function
- Photosynthetic Processes and Mechanisms
- Radiopharmaceutical Chemistry and Applications
- Organometallic Complex Synthesis and Catalysis
- Freezing and Crystallization Processes
- Radioactive Decay and Measurement Techniques
- DNA and Nucleic Acid Chemistry
- Biofuel production and bioconversion
- Advanced biosensing and bioanalysis techniques
- Superconducting Materials and Applications
- Plant Virus Research Studies
- Force Microscopy Techniques and Applications
- Inorganic Chemistry and Materials
- Medical Imaging and Pathology Studies
- Crystallography and molecular interactions
- Lipid metabolism and biosynthesis
MRC Laboratory of Molecular Biology
2010-2021
Medical Research Council
2007-2015
University of Cambridge
2010
U1 snRNP binds to the 5' exon-intron junction of pre-mRNA and thus plays a crucial role at an early stage splicing. We present two crystal structures engineered sub-structures, which together reveal atomic resolution almost complete network protein-protein RNA-protein interactions within snRNP, show how splice site is recognised by snRNP. The zinc-finger U1-C interacts with duplex between 5'-end snRNA. binding RNA stabilized hydrogen bonds electrostatic backbone around but makes no...
A human P spliceosome structure Splicing of some pre–messenger RNAs could be regulated by cell type–specific splicing factors. Fica et al. describe the cryo–electron microscopy postcatalytic (P) spliceosome. Surprisingly, it lacks factor Prp18, which plays an essential role in exon ligation yeast Instead, a metazoan-specific factor, FAM32A, compensates for Prp18 and promotes penetrating active sites directly stapling 5′ 3′ splice site. These findings suggest way to control tissue-specific...
Abstract RNA helicases remodel the spliceosome to enable pre-mRNA splicing, but their binding and mechanism of action remain poorly understood. To define helicase-RNA contacts in specific spliceosomal states, we develop purified iCLIP (psiCLIP), which reveals dynamic during splicing catalysis. The helicase Prp16 binds along entire available single-stranded region between branchpoint 3′-splice site, while Prp22 diffusely downstream before exon ligation, then switches more narrow after arguing...
The core domain of small nuclear ribonucleoprotein (snRNP), comprised a ring seven paralogous proteins bound around single-stranded RNA sequence, functions as the assembly nucleus in maturation U1, U2, U4 and U5 spliceosomal snRNPs. structure human snRNP was initially solved at 3.6 Å resolution by experimental phasing using data with tetartohedral twinning. Molecular replacement from this model followed density modification untwinned recently led to minimal U1 3.3 resolution. With latter...
Spliceosomal proteins Hsh49p and Cus1p are components of SF3b, which together with SF3a, Msl1p/Lea1p, Sm proteins, U2 snRNA, form snRNP, plays a crucial role in pre-mRNA splicing. Hsh49p, comprising two RRMs, forms heterodimer Cus1p. We determined the crystal structures Saccharomyces cerevisiae full-length as well its RRM1 complex minimal binding region (residues 290–368). The show that Cus1 fragment binds to α-helical surface RRM1, opposite four-stranded β-sheet, leaving canonical...