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Spliceozymes: Ribozymes that Remove Introns from Pre-mRNAs in Trans
Group I introns are pre-mRNA introns that do not require the spliceosome for their removal. Instead, they fold into complex three-dimensional structures and catalyze two transesterification reactions, thereby excising themselves and joining the flanking exons. These catalytic RNAs (ribozymes) have b...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094466/ https://www.ncbi.nlm.nih.gov/pubmed/25014025 http://dx.doi.org/10.1371/journal.pone.0101932 |
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author | Amini, Zhaleh N. Olson, Karen E. Müller, Ulrich F. |
author_facet | Amini, Zhaleh N. Olson, Karen E. Müller, Ulrich F. |
author_sort | Amini, Zhaleh N. |
collection | PubMed |
description | Group I introns are pre-mRNA introns that do not require the spliceosome for their removal. Instead, they fold into complex three-dimensional structures and catalyze two transesterification reactions, thereby excising themselves and joining the flanking exons. These catalytic RNAs (ribozymes) have been modified previously to work in trans, whereby the ribozymes can recognize a splice site on a substrate RNA and replace the 5′- or 3′-portion of the substrate. Here we describe a new variant of the group I intron ribozyme from Tetrahymena that recognizes two splice sites on a substrate RNA, removes the intron sequences between the splice sites, and joins the flanking exons, analogous to the action of the spliceosome. This ‘group I spliceozyme’ functions in vitro and in vivo, and it is able to mediate a growth phenotype in E. coli cells. The intron sequences of the target pre-mRNAs are constrained near the splice sites but can carry a wide range of sequences in their interior. Because the splice site recognition sequences can be adjusted to different splice sites, the spliceozyme may have the potential for wide applications as tool in research and therapy. |
format | Online Article Text |
id | pubmed-4094466 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40944662014-07-15 Spliceozymes: Ribozymes that Remove Introns from Pre-mRNAs in Trans Amini, Zhaleh N. Olson, Karen E. Müller, Ulrich F. PLoS One Research Article Group I introns are pre-mRNA introns that do not require the spliceosome for their removal. Instead, they fold into complex three-dimensional structures and catalyze two transesterification reactions, thereby excising themselves and joining the flanking exons. These catalytic RNAs (ribozymes) have been modified previously to work in trans, whereby the ribozymes can recognize a splice site on a substrate RNA and replace the 5′- or 3′-portion of the substrate. Here we describe a new variant of the group I intron ribozyme from Tetrahymena that recognizes two splice sites on a substrate RNA, removes the intron sequences between the splice sites, and joins the flanking exons, analogous to the action of the spliceosome. This ‘group I spliceozyme’ functions in vitro and in vivo, and it is able to mediate a growth phenotype in E. coli cells. The intron sequences of the target pre-mRNAs are constrained near the splice sites but can carry a wide range of sequences in their interior. Because the splice site recognition sequences can be adjusted to different splice sites, the spliceozyme may have the potential for wide applications as tool in research and therapy. Public Library of Science 2014-07-11 /pmc/articles/PMC4094466/ /pubmed/25014025 http://dx.doi.org/10.1371/journal.pone.0101932 Text en © 2014 Amini et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Amini, Zhaleh N. Olson, Karen E. Müller, Ulrich F. Spliceozymes: Ribozymes that Remove Introns from Pre-mRNAs in Trans |
title | Spliceozymes: Ribozymes that Remove Introns from Pre-mRNAs in Trans |
title_full | Spliceozymes: Ribozymes that Remove Introns from Pre-mRNAs in Trans |
title_fullStr | Spliceozymes: Ribozymes that Remove Introns from Pre-mRNAs in Trans |
title_full_unstemmed | Spliceozymes: Ribozymes that Remove Introns from Pre-mRNAs in Trans |
title_short | Spliceozymes: Ribozymes that Remove Introns from Pre-mRNAs in Trans |
title_sort | spliceozymes: ribozymes that remove introns from pre-mrnas in trans |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094466/ https://www.ncbi.nlm.nih.gov/pubmed/25014025 http://dx.doi.org/10.1371/journal.pone.0101932 |
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