Biogenesis and Transcriptional Regulation of Long Noncoding RNAs in the Human Immune System

The central dogma of molecular biology states that DNA makes RNA makes protein. Discoveries over the last quarter of a century found that the process of DNA transcription into RNA gives rise to a diverse array of functional RNA species, including genes that code for protein and noncoding RNAs. For decades, the focus has been on understanding how protein-coding genes are regulated to influence protein expression. However, with the completion of the Human Genome Project and follow-up ENCODE data, it is now appreciated that only 2-3% of the genome codes for protein-coding gene exons and that the bulk of the transcribed genome, apart from ribosomal RNAs, is at the level of noncoding RNA genes. In this article, researchers from the Vanderbilt University School of Medicine discuss the biogenesis and regulation of a distinct class of noncoding RNA molecules termed long, noncoding RNAs in the context of the immune system.

lncRNA and eRNA architecture


(A) eRNAs (red exons) are transcribed in one direction (1d-eRNA) or two directions (2d-eRNA) in close genome proximity to known protein-coding genes. Divergent lncRNAs (blue exons) are transcribed in the opposite direction from known protein-coding genes. Overlapping RNAs (purple exons) encompass the entirety of protein-coding genes in an intron region of the full-length lncRNA transcript. (B) Intronic lncRNAs (green exons) fall within an intron of a protein-coding gene. Sense and antisense lncRNAs (gold exons) are transcribed along the same (sense) or opposite (antisense) strand of the protein-coding gene. Exons from antisense lncRNAs are often partially shared. (C) Intergenic lincRNAs (pink exons) fall between known protein-coding genes and often regulate expression of these nearby mRNAs. (A–C) Gray arrows indicate the direction of gene transcription. Square boxes represent gene exons that are spliced to form mature transcripts for the indicated RNA species. PC, protein-coding gene.

Spurlock CF 3rd, Crooke PS 3rd, Aune TM. (2016) Biogenesis and Transcriptional Regulation of Long Noncoding RNAs in the Human Immune System. J Immunol 197(12):4509-4517. [abstract]

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