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      A View of Pre-mRNA Splicing from RNase R Resistant RNAs

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          Abstract

          During pre-mRNA splicing, exons in the primary transcript are precisely connected to generate an mRNA. Intron lariat RNAs are formed as by-products of this process. In addition, some exonic circular RNAs (circRNAs) may also result from exon skipping as by-products. Lariat RNAs and circRNAs are both RNase R resistant RNAs. RNase R is a strong 3' to 5' exoribonuclease, which efficiently degrades linear RNAs, such as mRNAs and rRNAs; therefore, the circular parts of lariat RNAs and the circRNAs can be segregated from eukaryotic total RNAs by their RNase R resistance. Thus, RNase R resistant RNAs could provide unexplored splicing information not available from mRNAs. Analyses of these RNAs identified repeating splicing phenomena, such as re-splicing of mature mRNAs and nested splicing. Moreover, circRNA might function as microRNA sponges. There is an enormous variety of endogenous circRNAs, which are generally synthesized in cells and tissues.

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          Transcriptome-wide discovery of circular RNAs in Archaea

          Miri Danan-Gotthold, Schraga Schwartz, Sarit Edelheit … (2011)
          Circular RNA forms had been described in all domains of life. Such RNAs were shown to have diverse biological functions, including roles in the life cycle of viral and viroid genomes, and in maturation of permuted tRNA genes. Despite their potentially important biological roles, discovery of circular RNAs has so far been mostly serendipitous. We have developed circRNA-seq, a combined experimental/computational approach that enriches for circular RNAs and allows profiling their prevalence in a whole-genome, unbiased manner. Application of this approach to the archaeon Sulfolobus solfataricus P2 revealed multiple circular transcripts, a subset of which was further validated independently. The identified circular RNAs included expected forms, such as excised tRNA introns and rRNA processing intermediates, but were also enriched with non-coding RNAs, including C/D box RNAs and RNase P, as well as circular RNAs of unknown function. Many of the identified circles were conserved in Sulfolobus acidocaldarius, further supporting their functional significance. Our results suggest that circular RNAs, and particularly circular non-coding RNAs, are more prevalent in archaea than previously recognized, and might have yet unidentified biological roles. Our study establishes a specific and sensitive approach for identification of circular RNAs using RNA-seq, and can readily be applied to other organisms.
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            Circular RNAs: splicing's enigma variations.

            Matthias W Hentze, Thomas Preiss (2013)
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              Splicing with inverted order of exons occurs proximal to large introns.

              C Cocquerelle, P Daubersies, M A Majérus … (1992)
              Following our studies which showed that the alpha and beta exons of the chicken c-ets-1 gene are not conserved in the human homologue, we succeeded in identifying a novel human c-ets-1 transcript in which the normal order of exons is scrambled. By PCR and RNase protection assays, we demonstrated that while the order of exons is different from that in genomic DNA, splicing of these exons in aberrant order occurs in pairs and at the same conserved consensus splice sites used in the normally spliced transcript. The scrambled transcript is non-polyadenylated and is expressed at much lower levels than the normal transcript. It is not the consequence of genomic rearrangement at the ets-1 locus nor is it due to the transcription of any ets-1 pseudogene. These results confirm previous observations of scrambled splicing.
              Article 0 comments Cited 126 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date (Electronic): 26 May 2014
                Publication date Collection: June 2014
                Volume: 15
                Issue: 6
                Pages: 9331-9342
                Affiliations
                [1 ]Center for Nano Materials and Technology, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1292, Japan
                [2 ]School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1292, Japan; E-Mail: tukahara@ 123456jaist.ac.jp
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: suzuki-h@ 123456jaist.ac.jp ; Tel.: +81-761-51-1643; Fax: +81-761-51-1455.
                Article
                Publisher ID: ijms-15-09331
                DOI: 10.3390/ijms15069331
                PMC ID: 4100097
                PubMed ID: 24865493
                SO-VID: ece27818-f4b2-4b61-bda1-7d971f93b40a
                Copyright © © 2014 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 08 April 2014
                Date revision received : 08 May 2014
                Date accepted : 16 May 2014
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular biology
                Keywords: pre-mrna splicing,rnase r,circular rna,multiexon skipping
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: pre-mrna splicing, rnase r, circular rna, multiexon skipping

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