Identification of expressed and conserved human noncoding RNAs

TY - JOUR

T1 - Identification of expressed and conserved human noncoding RNAs

AU - Nielsen, Morten Muhlig

AU - Tehler, Disa

AU - Vang, Søren

AU - Sudzina, Frantisek

AU - Hedegaard, Jakob

AU - Nordentoft, Iver

AU - Orntoft, Torben Falck

AU - Lund, Anders H.

AU - Pedersen, Jakob Skou

PY - 2014/2

Y1 - 2014/2

N2 - The past decade has shown mammalian genomes to be pervasively transcribed and identified thousands of noncoding (nc) transcripts. It is currently unclear to what extent these transcripts are of functional importance, as experimental functional evidence exists for only a small fraction. Here, we characterize the expression and evolutionary conservation properties of 12,115 known and novel nc transcripts, including structural RNAs, long nc RNAs (lncRNAs), antisense RNAs, EvoFold predictions, ultraconserved elements, and expressed nc regions. Expression levels are evaluated across 12 human tissues using a custom-designed microarray, supplemented with RNAseq. Conservation levels are evaluated at both the base level and at the syntenic level. We combine these measures with epigenetic mark annotations to identify subsets of novel nc transcripts that show characteristics similar to known functional ncRNAs. Few novel nc transcripts show both high expression and conservation levels. However, overall, we observe a positive correlation between expression and both conservation and epigenetic annotations, suggesting that a subset of the expressed transcripts are under purifying selection and likely functional. The identified subsets of expressed and conserved novel nc transcripts may form the basis for further functional characterization.

AB - The past decade has shown mammalian genomes to be pervasively transcribed and identified thousands of noncoding (nc) transcripts. It is currently unclear to what extent these transcripts are of functional importance, as experimental functional evidence exists for only a small fraction. Here, we characterize the expression and evolutionary conservation properties of 12,115 known and novel nc transcripts, including structural RNAs, long nc RNAs (lncRNAs), antisense RNAs, EvoFold predictions, ultraconserved elements, and expressed nc regions. Expression levels are evaluated across 12 human tissues using a custom-designed microarray, supplemented with RNAseq. Conservation levels are evaluated at both the base level and at the syntenic level. We combine these measures with epigenetic mark annotations to identify subsets of novel nc transcripts that show characteristics similar to known functional ncRNAs. Few novel nc transcripts show both high expression and conservation levels. However, overall, we observe a positive correlation between expression and both conservation and epigenetic annotations, suggesting that a subset of the expressed transcripts are under purifying selection and likely functional. The identified subsets of expressed and conserved novel nc transcripts may form the basis for further functional characterization.

KW - Base Sequence

KW - Chromatin

KW - Conserved Sequence

KW - Expressed Sequence Tags

KW - Humans

KW - Inverted Repeat Sequences

KW - Molecular Sequence Annotation

KW - Oligonucleotide Array Sequence Analysis

KW - Open Reading Frames

KW - Organ Specificity

KW - RNA, Untranslated

KW - Transcriptome

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1261/rna.038927.113

DO - 10.1261/rna.038927.113

M3 - Journal article

C2 - 24344320

SN - 1355-8382

VL - 20

SP - 236

EP - 251

JO - R N A

JF - R N A

IS - 2

ER -