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Post-transcriptional processing generates a diversity of 5′-modified long and short RNAs

Fejes-Tóth, Katalin and Sotirova, Vihra and Sachidanandam, Ravi and Assaf, Gordon and Hannon, Gregory J. and Kapranov, Philipp and Foissac, Sylvain and Willingham, Aarron T. and Duttagupta, Radha and Dumais, Erica and Gingeras, Thomas R. (2009) Post-transcriptional processing generates a diversity of 5′-modified long and short RNAs. Nature, 457 (7232). pp. 1028-1032. ISSN 0028-0836. PMCID PMC2719882. https://resolver.caltech.edu/CaltechAUTHORS:20200416-155025982

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Abstract

The transcriptomes of eukaryotic cells are incredibly complex. Individual non-coding RNAs dwarf the number of protein-coding genes, and include classes that are well understood as well as classes for which the nature, extent and functional roles are obscure. Deep sequencing of small RNAs (<200 nucleotides) from human HeLa and HepG2 cells revealed a remarkable breadth of species. These arose both from within annotated genes and from unannotated intergenic regions. Overall, small RNAs tended to align with CAGE (cap-analysis of gene expression) tags, which mark the 5′ ends of capped, long RNA transcripts. Many small RNAs, including the previously described promoter-associated small RNAs, appeared to possess cap structures. Members of an extensive class of both small RNAs and CAGE tags were distributed across internal exons of annotated protein coding and non-coding genes, sometimes crossing exon–exon junctions. Here we show that processing of mature mRNAs through an as yet unknown mechanism may generate complex populations of both long and short RNAs whose apparently capped 5′ ends coincide. Supplying synthetic promoter-associated small RNAs corresponding to the c-MYC transcriptional start site reduced MYC messenger RNA abundance. The studies presented here expand the catalogue of cellular small RNAs and demonstrate a biological impact for at least one class of non-canonical small RNAs.


Item Type:Article
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https://doi.org/10.1038/nature07759DOIArticle
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2719882PubMed CentralArticle
ORCID:
AuthorORCID
Fejes-Tóth, Katalin0000-0001-6558-2636
Additional Information:© 2009 Macmillan Publishers Limited. Received 16 September 2008; Accepted 02 January 2009; Published 25 January 2009. We thank L. Cardone, D. Rebolini, M. Kramer, and W. R. McCombie for Illumina sequencing. We wish to thank J. Brosius, J. Schmitz and T. Rozhdestvensky for their help with the small RNA cloning protocol and J. Dumais for technical assistance. K.F.-T. was in part supported by the Schering Foundation. This work was supported in part by grants from the NIH and was performed as part of the ENCODE consortium (G.J.H. and T.R.G.). G.J.H is an investigator of the Howard Hughes Medical Institute. Author Contributions: K.F.-T. and P.K. performed experiments in collaboration with E.D., V.S., R.D. and A.T.W. P.K., S.F., R.S. and G.A. performed data analysis. G.J.H. and T.R.G. planned experiments and wrote the paper. Competing interests: R.D. is an employee of Affymetrix, which manufactures the tiling arrays used in the study.
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Funding AgencyGrant Number
Schering FoundationUNSPECIFIED
NIHUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:7232
PubMed Central ID:PMC2719882
Record Number:CaltechAUTHORS:20200416-155025982
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200416-155025982
Official Citation:Fejes-Toth, K., Sotirova, V., Sachidanandam, R. et al. Post-transcriptional processing generates a diversity of 5′-modified long and short RNAs. Nature 457, 1028–1032 (2009). https://doi.org/10.1038/nature07759
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102592
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:16 Apr 2020 23:02
Last Modified:16 Apr 2020 23:02

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