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Open AccessJournal ArticleDOI

Pseudouridines in spliceosomal snRNAs.

TLDR
Experimental data indicate that virtually all pseudouridines in U2 snRNA are functionally important, strongly suggesting that pseudoursouridylation is also a regulatory modification.
Abstract
Spliceosomal RNAs are a family of small nuclear RNAs (snRNAs) that are essential for pre-mRNA splicing. All vertebrate spliceosomal snRNAs are extensively pseudouridylated after transcription. Pseudouridines in spliceosomal snRNAs are generally clustered in regions that are functionally important during splicing. Many of these modified nucleotides are conserved across species lines. Recent studies have demonstrated that spliceosomal snRNA pseudouridylation is catalyzed by two different mechanisms: an RNA-dependent mechanism and an RNA-independent mechanism. The functions of the pseudouridines in spliceosomal snRNAs (U2 snRNA in particular) have also been extensively studied. Experimental data indicate that virtually all pseudouridines in U2 snRNA are functionally important. Besides the currently known pseudouridines (constitutive modifications), recent work has also indicated that pseudouridylation can be induced at novel positions under stress conditions, thus strongly suggesting that pseudouridylation is also a regulatory modification.

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Journal ArticleDOI

Chemical pulldown reveals dynamic pseudouridylation of the mammalian transcriptome.

TL;DR: This work developed N3-CMC-enriched pseudouridine sequencing (CeU-Seq), a selective chemical labeling and pulldown method, to identify 2,084 Ψ sites within 1,929 human transcripts, of which four (in ribosomal RNA and EEF1A1 mRNA) are biochemically verified.
Journal ArticleDOI

Transcriptome-wide mapping of pseudouridines: pseudouridine synthases modify specific mRNAs in S. cerevisiae.

TL;DR: It is established that site-specific pseudouridylation of eukaryotic mRNAs is a genetically programmed RNA modification that naturally occurs in multiple yeast transcripts via distinct mechanisms, suggesting that mRNA pseudourIDylation may provide an important novel regulatory function.
Journal ArticleDOI

RNA pseudouridylation: new insights into an old modification

TL;DR: It has been reported that pseudouridine can be artificially introduced into mRNA by box H/ACA RNPs and that such introduction can mediate nonsense-to-sense codon conversion, thus demonstrating a new means of generating coding or protein diversity.
References
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Journal ArticleDOI

5-Fluorouracil: mechanisms of action and clinical strategies

TL;DR: This work has shown that novel genes identified in DNA microarray profiling have the potential to identify novel genes that are involved in mediating resistance to 5-FU, and these genes might prove to be therapeutically valuable as new targets for chemotherapy, or as predictive biomarkers of response to5-FU-based chemotherapy.
Journal Article

The RNA world

W. Gilbert
- 01 Jan 1986 - 
Journal ArticleDOI

Spliceosome structure and function.

TL;DR: The extensive interplay of RNA and proteins in aligning the pre-mRNA's reactive groups, and the presence of both RNA and protein at the core of the splicing machinery, suggest that the spliceosome is an RNP enzyme, but elucidation of the precise nature of its active site awaits the generation of a high-resolution structure of its RNP core.
Journal ArticleDOI

Spliced segments at the 5' terminus of adenovirus 2 late mRNA

TL;DR: Four segments of viral RNA may be joined together during the synthesis of mature hexon mRNA, a model is presented for adenovirus late mRNA synthesis that involves multiple splicing during maturation of a larger precursor nuclear RNA.
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