Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome

被引:405
作者
Ravasi, T
Suzuki, H
Pang, KC
Katayama, S
Furuno, M
Okunishi, R
Fukuda, S
Ru, KL
Frith, MC
Gongora, MM
Grimmond, SM
Hume, DA
Hayashizaki, Y
Mattick, JS [1 ]
机构
[1] Univ Queensland, Inst Mol Biosci, ARC Special Res Ctr Funct & Appl Genom, Brisbane, Qld 4072, Australia
[2] RIKEN, Riken Genom Sci Ctr, Yokohama Inst, Lab Genome Explorat Res Grp,Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan
[3] Ludwig Inst Canc Res, T Cell Lab, Austin & Repatriat Med Ctr, Melbourne, Vic 3084, Australia
关键词
D O I
10.1101/gr.4200206
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recent large-scale analyses of mainly full-length cDNA libraries generated from a variety of mouse tissues indicated that almost half of all representative cloned sequences did flat contain ail apparent protein-coding sequence, and were putatively derived from non-protein-coding RNA (ncRNA) genes. However, many of these clones were singletons and the majority were unspliced, raising the possibility that they may be derived from genomic DNA or unprocessed pre-rnRNA contamination during library construction, or alternatively represent nonspecific "transcriptional noise." Here we Show, using reverse transcriptase-dependent PCR, microarray, and Northern blot analyses, that many of these clones were derived from genuine transcripts Of unknown function whose expression appears to be regulated. The ncRNA transcripts have larger exons and fewer introns than protein-coding transcripts. Analysis of the genomic landscape around these sequences indicates that some cDNA clones were produced not from terminal poly(A) tracts but internal priming sites within longer transcripts, only a minority of which is encompassed by known genes. A significant proportion of these transcripts exhibit tissue-specific expression patterns, as well as dynamic changes in their expression in macrophages following lipopolysaccharide Stimulation. Taken together, the data provide strong support for the conclusion that ncRNAs are an important, regulated component of the mammalian transcriptome.
引用
收藏
页码:11 / 19
页数:9
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