Abstract
The involvement of noncoding RNAs (ncRNAs) in the development of the human brain remains largely unknown. Applying a cloning strategy for detection of intermediate size (50–500 nt) ncRNAs (is-ncRNAs) we have identified 82 novel transcripts in human fetal brain tissue. Most of the novel is-ncRNAs are not well conserved in vertebrates, and several transcripts were only found in primates. Northern blot and microarray analysis indicated considerable variation in expression across human fetal brain development stages and fetal tissues for both novel and known is-ncRNAs. Expression of several of the novel is-ncRNAs was conspicuously absent in one or two brain cancer cell lines, and transient overexpression of some transcripts in cancer cells significantly inhibited cell proliferation. Overall, our results suggest that is-ncRNAs play important roles in the development and tumorigenesis of human brain.
Highlights
It is increasingly becoming evident that a major part of the information content in eukaryote genomes is expressed in the form of non-protein-coding RNAs
Removal of sequences that represented annotated mRNAs, rRNAs and tRNAs from the altogether 20,539 sequenced clones left 17,723 transcripts corresponding to 326 unique sequences which could be mapped to 331 loci in the human genome (Figure 1A; Figure S1; Table S1)
Recent analysis have demonstrated that the central nervous system is among the tissues most enriched in expressed miRNAs [43] and long noncoding transcripts [1] in mammals
Summary
It is increasingly becoming evident that a major part of the information content in eukaryote genomes is expressed in the form of non-protein-coding RNAs (ncRNAs; [1]). The rat C/D box snoRNA RBII36 locus is situated within an intron of the noncoding RNA Bsr, and appears to be generated from both debranched intron-lariats as well as from endonucleolytic cleavage of the Bsr primary transcript [24] Another example of intermediate-size brain specific noncoding RNAs are the BC1 and BC200 transcripts found in rodents and primates, respectively. These transcripts have cytoplasmic neuronal expression patterns, including a concentration to dendrites [25,26] and axons [27]. We report a systematic identification and validation of 82 novel intermediate-size ncRNAs (is-ncRNAs) from human fetal brain These novel is-ncRNAs are generally not well conserved in vertebrates, and several loci are only found in primates. Our results provide new insights into the diversity of is-ncRNAs and their involvement in brain development and tumorigenesis
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