Macro lncRNAs

Long Noncoding RNAs in Imprinting and X Chromosome Inactivation

“…The Kcnq1 region is a well-studied ~800 kb imprinted locus located on human chromosome 11p15 and mouse chromosome 7 [32], with several maternally-expressed protein-coding genes (including Kcnq1 itself, coding for potassium voltage-gated channel, KQT-like subfamily, member 1), and a 60 kb paternally-expressed unspliced lncRNA Kcnq1 opposite strand/antisense transcript 1 ( Kcnq1ot1 ) that is antisense to an interior portion of Kncq1 and serves to silence it in cis , as well as nearby genes (bi-directionally) on the paternal chromosome (See Figure 3) [45,46,47]. This antisense noncoding RNA initiates transcription midway through the (sense) Kcnq1 gene, from a promoter in Intron 10 [16,45].…”

“…The Kcnq1ot1 promoter has in fact been determined to be the ICR of this imprinted region. It is methylated in oocytes, and subsequently, on the maternal allele in the embryo and extraembryonic tissues, to prevent expression of the Kcnq1ot1 lncRNA [33,47]. Paternal transmission of an ICR deletion results in no expression of Kcnq1ot1 and biallelic expression of the maternal genes in mice, while a maternally-inherited deletion has no effect on imprinting [16].…”

“…Igf2r / Airn is a medium-sized ~500 kb imprinted locus found on human chromosome 6q26 and mouse chromosome 17 [47] and shares many properties with the Kcnq1 imprinted locus—where a set of maternally-expressed protein-coding genes is silenced on the paternal chromosome in cis by a paternally-expressed lncRNA that is antisense to one of the central maternal genes. While Igf2r is imprinted in mice, and has been shown to be maternally hypermethylated in a CpG island in humans, it is biallelically expressed in almost all tissues examined [84,85,86], with the exception that monoallelic expression has been noted in rare fetal samples [87,88] and samples from Wilm’s tumors [89].…”

A role for chromatin topology in imprinted domain regulation

“…Imprinted lncRNAs range in length from ϳ1.6 kb to ϳ1000 kb, and thus, many imprinted lncRNAs are also classified as macro lncRNAs due to their extraordinary length (Guenzl and Barlow 2012). To date, seven imprinted lncRNAs have been identified that are regulated by imprinted gDMRs and are conserved between mice and humans: Airn, Gtl2, H19, Kcnq1ot1, Nespas, Peg13, and Ube3a-as (Brannan et al 1990;Gray et al 1999;Smilinich et al 1999;Lyle et al 2000;Paulsen et al 2001;Coombes et al 2003;Court et al 2014).…”

Non-coding RNA and disease

“…14 Macro lncRNAs can affect imprinting or gene expression in cis, 15 while the telomeric repeat containing TERRA transcripts regulate telomere function and hence affect the development of telomere syndromes or cancer. 16 Research on microRNAs has been greatly facilitated by their common mechanism: They commonly function in posttranscriptional gene regulation, thus determination of their target genes at the mRNA or the protein level has often uncovered their physiological and pathological functions.…”