Identification of human short introns

Canonical pre-mRNA splicing requires snRNPs and associated splicing factors to excise conserved intronic sequences, with a minimum intron length required for efficient splicing. Non-canonical splicing-intron excision without the spliceosome-has been documented; most notably, some tRNAs and the XBP1...

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Published in:	PloS one Vol. 12; no. 5; p. e0175393
Main Authors:	Abebrese, Emmanuel L, Ali, Syed H, Arnold, Zachary R, Andrews, Victoria M, Armstrong, Katharine, Burns, Lindsay, Crowder, Hannah R, Day, Jr, R Thomas, Hsu, Daniel G, Jarrell, Katherine, Lee, Grace, Luo, Yi, Mugayo, Daphine, Raza, Zain, Friend, Kyle
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 17-05-2017 Public Library of Science (PLoS)
Subjects:	Activating transcription factor 1 Algorithms Alignment Alternative splicing Biochemistry Biology and Life Sciences Burns Cell culture Cell fate Cell Line Chemistry Chromatin Circular RNA Circularity Coding Conserved sequence Contamination Cyclic AMP response element-binding protein Cytoplasm Decay Deoxyribonucleic acid DNA Endonuclease Enzymes Exons Gene sequencing Genes Genetic regulation Genetic research Genome, Human Genomes Gold Homology Humans Introns Iron Mammals Messenger RNA Nuclei Nucleic acids Nucleotides Open Reading Frames Phosphates Position (location) Properties Protein structure Proteins Research and Analysis Methods Ribonucleic acid RNA RNA Splicing RNA, Messenger - chemistry RNA, Messenger - genetics RNA, Transfer - chemistry RNA, Transfer - genetics Sequence Analysis, RNA - methods Sequence Deletion Splicing factors Tissue culture Translation X-Box Binding Protein 1 - genetics Yeast United States > US Virginia
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Summary:	Canonical pre-mRNA splicing requires snRNPs and associated splicing factors to excise conserved intronic sequences, with a minimum intron length required for efficient splicing. Non-canonical splicing-intron excision without the spliceosome-has been documented; most notably, some tRNAs and the XBP1 mRNA contain short introns that are not removed by the spliceosome. There have been some efforts to identify additional short introns, but little is known about how many short introns are processed from mRNAs. Here, we report an approach to identify RNA short introns from RNA-Seq data, discriminating against small genomic deletions. We identify hundreds of short introns conserved among multiple human cell lines. These short introns are often alternatively spliced and are found in a variety of RNAs-both mRNAs and lncRNAs. Short intron splicing efficiency is increased by secondary structure, and we detect both canonical and non-canonical short introns. In many cases, splicing of these short introns from mRNAs is predicted to alter the reading frame and change protein output. Our findings imply that standard gene prediction models which often assume a lower limit for intron size fail to predict short introns effectively. We conclude that short introns are abundant in the human transcriptome, and short intron splicing represents an added layer to mRNA regulation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: The authors have declared that no competing interests exist. Conceptualization: ELA SHA VMA KA ZRA LB HRC RTD DGH KJ GL YL DM ZR KF.Data curation: ELA SHA VMA KA ZRA LB HRC RTD DGH KJ GL YL DM ZR KF.Formal analysis: ELA SHA VMA KA ZRA LB HRC RTD DGH KJ GL YL DM ZR KF.Funding acquisition: KF.Investigation: KF.Methodology: ELA SHA VMA KA ZRA LB HRC RTD DGH KJ GL YL DM ZR KF.Project administration: KF.Resources: KF.Software: KF.Supervision: KF.Validation: ELA SHA VMA KA ZRA LB HRC RTD DGH KJ GL YL DM ZR KF.Visualization: KF.Writing – original draft: ELA SHA VMA KA ZRA LB HRC RTD DGH KJ GL YL DM ZR KF.Writing – review & editing: ELA SHA VMA KA ZRA LB HRC RTD DGH KJ GL YL DM ZR KF.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0175393