Abstract
Long non-coding RNAs (lncRNAs) as a key group of non-coding RNAs have gained widely attention. Though lncRNAs have been functionally annotated and systematic explored in higher mammals, few are under systematical identification and annotation. Owing to the expression specificity, known lncRNAs expressed in embryonic brain tissues remain still limited. Considering a large number of lncRNAs are only transcribed in brain tissues, studies of lncRNAs in developmental brain are therefore of special interest. Here, publicly available RNA-sequencing (RNA-seq) data in embryonic brain are integrated to identify thousands of embryonic brain lncRNAs by a customized pipeline. A significant proportion of novel transcripts have not been annotated by available genomic resources. The putative embryonic brain lncRNAs are shorter in length, less spliced and show less conservation than known genes. The expression of putative lncRNAs is in one tenth on average of known coding genes, while comparable with known lncRNAs. From chromatin data, putative embryonic brain lncRNAs are associated with active chromatin marks, comparable with known lncRNAs. Embryonic brain expressed lncRNAs are also indicated to have expression though not evident in adult brain. Gene Ontology analysis of putative embryonic brain lncRNAs suggests that they are associated with brain development. The putative lncRNAs are shown to be related to possible cis-regulatory roles in imprinting even themselves are deemed to be imprinted lncRNAs. Re-analysis of one knockdown data suggests that four regulators are associated with lncRNAs. Taken together, the identification and systematic analysis of putative lncRNAs would provide novel insights into uncharacterized mouse non-coding regions and the relationships with mammalian embryonic brain development.
Highlights
Recent transcriptomic researches have revealed that a significant fraction of genome can transcribe non-coding RNAs, the proportion of which is much larger than previously anticipated [1,2]
To systematically discover novel long non-coding RNAs (lncRNAs) with potential regulatory functions in embryonic brain, we collected a set of 17 mRNA-seq datasets (Table S1) involving three stages that mark important developmental time points/stages: (1) Embryonic day 14.5 (E14) brain; (2) Embryonic day 15.5 (E15) brain and (3) Embryonic day 17.5 (E17) brain
We evaluated if putative Transcription Start Sites (TSSs) of putative embryonic brain lncRNAs tended to close to any CAGE clusters which were representative of potential TSSs
Summary
Recent transcriptomic researches have revealed that a significant fraction of genome can transcribe non-coding RNAs (ncRNAs), the proportion of which is much larger than previously anticipated [1,2]. In the ncRNA world, long non-coding RNAs (lncRNAs) which are manually defined by their size (at least 200 nt) are a distinct group from small RNAs (,200 nt, such as miRNAs and siRNAs). LncRNAs have diverse roles in genomic regulation, involving transcriptional regulation, imprinting and epigenetic regulation [7,8,9]. LncRNA HOTAIR expressed from HOXC cluster is shown to epigenetically repress the HOXD locus by involvement of the PRC2 complex [14]. Imprinted lncRNAs, such as Rian and Mirg [15,16,17], can be precursors of small RNAs such as snoRNAs and miRNAs
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