Do repeated arrays of regulatory small‐RNA genes elicit genomic imprinting?

Abstract

The basic premise of the host-defense theory is that genomic imprinting, the parent-of-origin expression of a subset of mammalian genes, derives from mechanisms originally dedicated to silencing repeated and retroviral-like sequences that deeply colonized mammalian genomes. We propose that large clusters of tandemly-repeated C/D-box small nucleolar RNAs (snoRNAs) or microRNAs represent a novel category of sequences recognized as "genomic parasites", contributing to the emergence of genomic imprinting in a subset of chromosomal regions that contain them. Such a view is supported by evidence derived from studies of the imprinted snoRNA- and/or miRNA-encoding Dlk1-Dio3, Snurf-Snrpn, Sfbmt2, and C19MC domains. While adding a new piece to the challenging puzzle of mammalian genome history, this hypothesis also reinforces the notion that dissecting the features and molecular mechanisms that discriminate between "foreign" and "endogenous" sequences is of crucial importance in the field of mammalian epigenetics.

Small regulatory RNAs controlled by genomic imprinting and their contribution to human disease

“…This striking phenomenon is the focus of the current review. Almost seven percent of the known human microRNAs are encoded by imprinted domains 3 and nowhere in the genome there is such a high density of small regulatory RNAs as at imprinted domains, some of which comprise more than 50 small RNAs per Mb. The regulation and roles of imprinted small RNAs are actively being explored by many laboratories.…”

“…No fewer than 107 imprinted microRNAs and 117 imprinted snoRNAs have been identified to date (www.mirbase.org; www-snorna.biotoul.fr). Most of these are organized in large transcriptional units, each producing multiple, highly related small RNAs 3 . In the human genome, six imprinted domains comprise transcription units that generate small regulatory RNAs.…”

Comment on “Do repeated arrays of box C/D small nucleolar RNA and microRNA genes elicit genomic imprinting?” DOI 10.1002/bies201100032

“…Since some human disorders, including the Beckwith-Wiedeman, SilverRussell, Prader-Willi, and Angelman syndromes, occur due to the loss of function of imprinted genes, understanding the evolutionary reason(s) for genomic imprinting is an interesting and medically relevant topic. In this issue, Labialle and Cavaillé posit that large clusters of small non-coding RNAs contributed to the acquisition of the genomic imprint in the chromosomal regions in which they reside [1]. They provide four examples of tandemly repeated small RNA clusters that are controlled by genomic imprinting and discuss the idea that the acquisition of differential DNA methylation was likely to have been concurrent with the invasion of the small RNA genes.…”

“…While the murine host genes become imprinted, imprinting was very recently shown to be lost at the host loci in humans and distinct from the imprinting mechanisms that regulate large clusters (i.e. Snurf-Snrpn and Dlk1-Dio3 clusters) of imprinted genes [1].…”

BioEssays in non‐coding RNAs: A special collection of recent content

“…And it is not only in CNS injury that non-coding RNAs play an important role in the brain: the mammalian brain and placenta manifest particularly high expression of imprinted genes, a phenomenon that is orchestrated by regulatory small-RNAs. In a hypothesis article, Labialle and Cavaillé propose that subclasses of these RNAs -recognised as ''genomic parasites'' -have contributed to the emergence of genomic imprinting by virtue of their occurrence in huge repeat arrays [6]. In general, non-coding transcripts, including long non-coding RNA sequences, reside in juxtaposition with gene clusters in imprinted domains of chromosomes.…”