Abstract
The U2 small nuclear ribonucleoprotein (snRNP) is an essential component of the spliceosome, the cellular machine responsible for removing introns from precursor mRNAs (pre-mRNAs) in all eukaryotes. U2 is an extraordinarily dynamic splicing factor and the most frequently mutated in cancers. Cryo-electron microscopy (cryo-EM) has transformed our structural and functional understanding of the role of U2 in splicing. In this review, we synthesize these and other data with respect to a view of U2 as an assembly of interconnected functional modules. These modules are organized by the U2 small nuclear RNA (snRNA) for roles in spliceosome assembly, intron substrate recognition, and protein scaffolding. We describe new discoveries regarding the structure of U2 components and how the snRNP undergoes numerous conformational and compositional changes during splicing. We specifically highlight large scale movements of U2 modules as the spliceosome creates and rearranges its active site. U2 serves as a compelling example for how cellular machines can exploit the modular organization and structural plasticity of an RNP.
🔬 Techniques
🧬 Organisms
🧪 Sample Preparation
🔬 Cell Lines
💻 Software Details
💾 Data Repositories
🏛️ Research Organizations (ROR)
Affiliated research institutions:
📊 Figures
Figure 1.
Overview of the stages of pre-mRNA splicing. The spliceosome catalyzes splicing of the pre-mRNA by recognition of the 5u02b9 SS, BS, and the 3u02b9 SS. Many steps are required for excision of the intr...
Figure 2.
Sequences and secondary structures of the conserved modules of the yeast ( A ) and human ( B ) U2 snRNAs. The modules consist of the Stem I (pink), branch point recognition sequence (BPRS, green), Ste...
Figure 3.
Organization of the protein components of the U2 snRNP in the spliceosome B complex (PDB ID:5NRL). The BPRS, Stem II, and Sm binding site/3u02b9 stem loop modules of U2 snRNA (green) scaffold an arran...
Figure 4.
Pairing between the U2 stem I module and the U6 snRNA in the spliceosome. ( A ) 2D schematic of U2/U6 helices Ia (light blue), Ib (navy) and II (purple) in the spliceosome prior to 5u02b9 SS cleavage....
Figure 5.
Structure of the U2/BS duplex and its RNA interactions during splicing. ( A ) Schematic of the U2/BS RNA duplex. U2 snRNA (green) pairs to the branch site (black) resulting in expulsion of the branch ...
Figure 6.
Structure of the human U2 protein SF3B1. ( A ) Domain organization of human SF3B1. HEAT repeats 4u20137 (green) is hot spot for mutations associated a variety of cancers. HEAT repeats 15 and 16 (black...
Figure 7.
Movements of the U2/BS duplex during splicing. ( A ) Movements of the duplex during B to B act to C complex transitions. Movements are shown in relation to the active site and U6 catalytic triplex (or...
Figure 8.
U2 Stem II dynamics during splicing. ( A ) Stem IIa (blue) is a mutually exclusive structure to stem IIc (blue/red). Stem IIb (lavender) can be accommodated by both stem IIa and IIb pairing. In the sp...
Figure 9.
Interactions between the U2 Sm ring and splicing factors in spliceosomes. The Sm binding site in U2 snRNA is shown in green. ( A ) Interaction between the SmD1 and SmD2 proteins and the SF3a protein P...
Figure 10.
Long-distance movements of the U2 BPRS, stem II, and 3u02b9 modules during splicing. ( A ) Yeast U2 snRNA (nt 1u2013105) movement as the spliceosome progresses from pre-B to ILS complex formation in t...
Figure images are served from the NIH/NLM PubMed Central Open Access Subset or Europe PMC; copyright remains with the publishers and authors.
💬 Discussion
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