Genetic Analysis of Human RNA Binding Motif Protein 48 (RBM48) Reveals an Essential Role in U12-Type Intron Splicing

Siebert, Amy E; Corll, Jacob; Gronevelt, J Paige; Levine, Laurel; Hobbs, Linzi M; Kenney, Catalina; Davenport, R. John; Settles, Alexander; Barbazuk, W. Brad; Westrick, Randal J.; Madlambayan, Gerard J.; Lal, Sadhna

doi:10.1101/2020.07.18.209528

Cited by 2 publications

(4 citation statements)

References 71 publications

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“…RBM48 is thought to be an essential splicing factor for U12-type introns, as its mutations cause abnormality in genome-wide U12-type splicing (47,48). Together with ARMC7, RBM48 binds the 5′-end of U6atac snRNA, which lacks the 5′-stem loop compared to U6 snRNA in the major spliceosome.…”

Section: Discussionmentioning

confidence: 99%

Section: The Rbm48-armc7 Complex Binds the 5′-end Of U6atac Snrnamentioning

confidence: 99%

“…The RNA binding motif (RRM) containing protein RBM48 is essential for splicing of U12-type introns in both plants and animals (47,48). It interacts with the protein armadillo repeat containing 7 (ARMC7) (47)(48)(49). RBM48-deficient human cell lines and maize endosperm display aberrant splicing of the U12-type introns, which may lead to developmental defects (47,48).…”

Section: The Rbm48-armc7 Complex Binds the 5′-end Of U6atac Snrnamentioning

confidence: 99%

“…It interacts with the protein armadillo repeat containing 7 (ARMC7) (47)(48)(49). RBM48-deficient human cell lines and maize endosperm display aberrant splicing of the U12-type introns, which may lead to developmental defects (47,48). However, the role of RBM48 in U12-dependent splicing remains unknown.…”

Section: The Rbm48-armc7 Complex Binds the 5′-end Of U6atac Snrnamentioning

confidence: 99%

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Structure of the activated human minor spliceosome

Bai

Wan

Wang

et al. 2021

Science

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The minor spliceosome mediates splicing of the rare but essential U12-type pre-mRNA. Here we report the atomic features of the activated human minor spliceosome determined by cryo-electron microscopy at 2.9-Å resolution. The 5′-splice site and branch point sequence of the U12-type intron are recognized by U6atac and U12 small nuclear RNA (snRNA), respectively. Five newly identified proteins stabilize the conformation of the catalytic center. The zinc finger protein SCNM1 functionally mimics the SF3a complex of the major spliceosome. The RBM48/ARMC7 complex binds the γ-monomethyl phosphate cap at the 5′-end of U6atac snRNA. The U-box protein PPIL2 coordinates loop I of U5 snRNA and stabilizes U5 snRNP. CRIPT stabilizes U12 snRNP. Our study provides a framework for mechanistic understanding of the function of the minor spliceosome.

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Section: Discussionmentioning

confidence: 99%

Section: The Rbm48-armc7 Complex Binds the 5′-end Of U6atac Snrnamentioning

confidence: 99%

Section: The Rbm48-armc7 Complex Binds the 5′-end Of U6atac Snrnamentioning

confidence: 99%

Section: The Rbm48-armc7 Complex Binds the 5′-end Of U6atac Snrnamentioning

confidence: 99%

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Structure of the activated human minor spliceosome

Bai

Wan

Wang

et al. 2021

Science

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Roles of minor spliceosome in intron recognition and the convergence with the better understood major spliceosome

et al. 2022

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Catalyzed by spliceosomes in the nucleus, RNA splicing removes intronic sequences from precursor RNAs in eukaryotes to generate mature RNA, which also significantly increases proteome complexity and fine-tunes gene expression. Most metazoans have two coexisting spliceosomes; the major spliceosome, which removes >99.5% of introns, and the minor spliceosome, which removes far fewer introns (only 770 at present have been predicted in the human genome). Both spliceosomes are large and dynamic machineries, each consisting of five small nuclear RNAs (snRNAs) and more than 100 proteins. However, the dynamic assembly, catalysis, and protein composition of the minor spliceosome are still poorly understood. With different splicing signals, minor introns are rare and usually distributed alone and flanked by major introns in genes, raising questions of how they are recognized by the minor spliceosome and how their processing deals with the splicing of neighboring major introns. Due to large numbers of introns and close similarities between the two machinery, cooperative, and competitive recognition by the two spliceosomes has been investigated. Functionally, many minor-intron-containing genes are evolutionarily conserved and essential. Mutations in the minor spliceosome exhibit a variety of developmental defects in plants and animals and are linked to numerous human diseases. Here, we review recent progress in the understanding of minor splicing, compare currently known components of the two spliceosomes, survey minor introns in a wide range of organisms, discuss cooperation and competition of the two spliceosomes in splicing of minor-intron-containing genes, and contributions of minor splicing mutations in development and diseases.

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Genetic Analysis of Human RNA Binding Motif Protein 48 (RBM48) Reveals an Essential Role in U12-Type Intron Splicing

Cited by 2 publications

References 71 publications

Structure of the activated human minor spliceosome

Structure of the activated human minor spliceosome

Roles of minor spliceosome in intron recognition and the convergence with the better understood major spliceosome

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