Unraveling the Complexity of the Human Spliceosome and RNA Splicing

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biomacromolecules: Nucleic Acids".

Deadline for manuscript submissions: closed (30 July 2024) | Viewed by 1403

Special Issue Editor


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Guest Editor
Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD 21218, USA
Interests: RNA-seq; alternative splicing; sequence alignment; gene annotation; miRNAs; computational biology; gene annotation; alternative splicing; genomics and transcriptomics

Special Issue Information

Dear Colleagues,

RNA splicing is a fundamental molecular process leading to the formation of functional mRNAs and proteins from a gene encoded in the DNA. Eukaryotic genes are interrupted, with coding DNA separated by intervening stretches of a non-coding sequence. The removal of the non-coding regions from the pre-mRNA transcripts, or splicing, is accomplished via a complex of small nuclear RNAs and proteins, forming the spliceosome. Significant advances have been made in determining the components of the spliceosome, its 3D structure, and how the accurate recognition and selection of splice sites takes place during splicing; however, questions remain, as these areas are under active investigation.

This Special Issue of Biomolecules aims to provide an overview of novel information and current research regarding the characterization of the human spliceosome and pre-mRNA splicing. Contributions in the form of original research papers and reviews that address the following topics are welcome: spliceosome organization, structure, and function; the regulation of RNA splicing; RNA splicing in human physiology and development; and the computational modeling of RNA splicing. However, studies related to the discovery and role of RNA splicing in disease, and technologies able to study RNA splicing and the spliceosome, are generally considered outside the scope of the Biomolecules journal.

Our aim is to provide a forum for investigators from around the globe to create a compendium of research efforts and advances in this fundamental area of molecular biology.

Dr. Liliana Florea
Guest Editor

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Keywords

  • spliceosome
  • splicing regulation
  • RNA splicing in human physiology and development
  • computational modelling

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Published Papers (1 paper)

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Research

14 pages, 2519 KiB  
Communication
Alternative Splicing of the Last TKFC Intron Yields Transcripts Differentially Expressed in Human Tissues That Code In Vitro for a Protein Devoid of Triokinase and FMN Cyclase Activity
by María Jesús Costas, Ana Couto, Alicia Cabezas, Rosa María Pinto, João Meireles Ribeiro and José Carlos Cameselle
Biomolecules 2024, 14(10), 1288; https://doi.org/10.3390/biom14101288 - 12 Oct 2024
Viewed by 977
Abstract
The 18-exon human TKFC gene codes for dual-activity triokinase and FMN cyclase (TKFC) in an ORF, spanning from exon 2 to exon 18. In addition to TKFC-coding transcripts (classified as tkfc type by their intron-17 splice), databases contain evidence for alternative TKFC transcripts, [...] Read more.
The 18-exon human TKFC gene codes for dual-activity triokinase and FMN cyclase (TKFC) in an ORF, spanning from exon 2 to exon 18. In addition to TKFC-coding transcripts (classified as tkfc type by their intron-17 splice), databases contain evidence for alternative TKFC transcripts, but none of them has been expressed, studied, and reported in the literature. A novel full-ORF transcript was cloned from brain cDNA and sequenced (accession no. DQ344550). It results from an alternative 3′ splice-site in intron 17. The cloned cDNA contains an ORF also spanning from exon 2 to exon 18 of the TKFC gene but with a 56-nt insertion between exons 17 and 18 (classified as tkfc_ins56 type). This insertion introduces an in-frame stop, and the resulting ORF codes for a shorter TKFC variant, which, after expression, is enzymatically inactive. TKFC intron-17 splicing was found to be differentially expressed in human tissues. In a multiple-tissue northern blot using oligonucleotide probes, the liver showed a strong expression of the tkfc-like splice of intron 17, and the heart preferentially expressed the tkfc_ins56-like splice. Through a comparison to global expression data from massive-expression studies of human tissues, it was inferred that the intestine preferentially expresses TKFC transcripts that contain neither of those splices. An analysis of transcript levels quantified by RNA-Seq in the GTEX database revealed an exception to this picture due to the occurrence of a non-coding short transcript with a tkfc-like splice. Altogether, the results support the occurrence of potentially relevant transcript variants of the TKFC gene, differentially expressed in human tissues. (This work is dedicated in memoriam to Professor Antonio Sillero, 1938–2024, for his lifelong mentoring and his pioneering work on triokinase). Full article
(This article belongs to the Special Issue Unraveling the Complexity of the Human Spliceosome and RNA Splicing)
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