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Open Access Highly Accessed Research article

Gene processing control loops suggested by sequencing, splicing, and RNA folding

Clark D Jeffries12*, Diana O Perkins3 and Xiaojun Guan4

Author Affiliations

1 Eshelman School of Pharmacy and Renaissance Computing Institute, University of North Carolina at Chapel Hill, NC, USA

2 Renaissance Computing Institute, University of North Carolina at Chapel Hill, NC, USA

3 Department of Psychiatry, University of North Carolina at Chapel Hill, NC, USA

4 Center for Bioinformatics, University of North Carolina at Chapel Hill, NC, USA

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BMC Bioinformatics 2010, 11:602  doi:10.1186/1471-2105-11-602

Published: 20 December 2010

Abstract

Background

Small RNAs are known to regulate diverse gene expression processes including translation, transcription, and splicing. Among small RNAs, the microRNAs (miRNAs) of 17 to 27 nucleotides (nts) undergo biogeneses including primary transcription, RNA excision and folding, nuclear export, cytoplasmic processing, and then bioactivity as regulatory agents. We propose that analogous hairpins from RNA molecules that function as part of the spliceosome might also be the source of small, regulatory RNAs (somewhat smaller than miRNAs).

Results

Deep sequencing technology has enabled discovery of a novel 16-nt RNA sequence in total RNA from human brain that we propose is derived from RNU1, an RNA component of spliceosome assembly. Bioinformatic alignments compel inquiring whether the novel 16-nt sequence or its precursor have a regulatory function as well as determining aspects of how processing intersects with the miRNA biogenesis pathway. Specifically, our preliminary in silico investigations reveal the sequence could regulate splicing factor Arg/Ser rich 1 (SFRS1), a gene coding an essential protein component of the spliceosome. All 16-base source sequences in the UCSC Human Genome Browser are within the 14 instances of RNU1 genes listed in wgEncodeGencodeAutoV3. Furthermore, 10 of the 14 instances of the sequence are also within a common 28-nt hairpin-forming subsequence of RNU1.

Conclusions

An abundant 16-nt RNA sequence is sourced from a spliceosomal RNA, lies in a stem of a predicted RNA hairpin, and includes reverse complements of subsequences of the 3'UTR of a gene coding for a spliceosome protein. Thus RNU1 could function both as a component of spliceosome assembly and as inhibitor of production of the essential, spliceosome protein coded by SFRS1. Beyond this example, a general procedure is needed for systematic discovery of multiple alignments of sequencing, splicing, and RNA folding data.