Imprinted Chromatin Around DIRAS3 Regulates Alternative Splicing of GNG12-AS1, a Long Noncoding RNA

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2013 Jul 23

PMID 23871723

Citations 23

Authors

Malwina Niemczyk

Yoko Ito

Joanna Huddleston

Anna Git

Sayeda Abu-Amero

Carlos Caldas

Gudrun E Moore

Lovorka Stojic

Adele Murrell

Affiliations

Soon will be listed here.

Abstract

Imprinted gene clusters are regulated by long noncoding RNAs (lncRNAs), CCCTC binding factor (CTCF)-mediated boundaries, and DNA methylation. DIRAS3 (also known as ARH1 or NOEY1) is an imprinted gene encoding a protein belonging to the RAS superfamily of GTPases and is located within an intron of a lncRNA called GNG12-AS1. In this study, we investigated whether GNG12-AS1 is imprinted and coregulated with DIRAS3. We report that GNG12-AS1 is coexpressed with DIRAS3 in several tissues and coordinately downregulated with DIRAS3 in breast cancers. GNG12-AS1 has several splice variants, all of which initiate from a single transcription start site. In placenta tissue and normal cell lines, GNG12-AS1 is biallelically expressed but some isoforms are allele-specifically spliced. Cohesin plays a role in allele-specific splicing of GNG12-AS1. In breast cancer cell lines with loss of DIRAS3 imprinting, DIRAS3 and GNG12-AS1 are silenced in cis and the remaining GNG12-AS1 transcripts are predominantly monoallelic. The GNG12-AS1 locus, which includes DIRAS3, provides an example of imprinted cotranscriptional splicing and a potential model system for studying the long-range effects of CTCF-cohesin binding on splicing and transcriptional interference.

Citing Articles

Differential 3D genome architecture and imprinted gene expression: cause or consequence?.

Moindrot B, Imaizumi Y, Feil R Biochem Soc Trans. 2024; 52(3):973-986.

PMID: 38775198 PMC: 11346452. DOI: 10.1042/BST20230143.

Long non-coding RNAs PTENP1, GNG12-AS1, MAGI2-AS3 and MEG3 as tumor suppressors in breast cancer and their associations with clinicopathological parameters.

Zavesky L, Jandakova E, Weinberger V, Minar L, Kohoutova M, Slanar O Cancer Biomark. 2024; 40(1):61-78.

PMID: 38277283 PMC: 11191509. DOI: 10.3233/CBM-230259.

Imprinted Long Non-Coding RNAs in Mammalian Development and Disease.

Di Michele F, Chillon I, Feil R Int J Mol Sci. 2023; 24(17).

PMID: 37686455 PMC: 10487962. DOI: 10.3390/ijms241713647.

Interplay between LncRNAs and microRNAs in Breast Cancer.

Schwarzenbach H, Gahan P Int J Mol Sci. 2023; 24(9).

PMID: 37175800 PMC: 10179369. DOI: 10.3390/ijms24098095.

Widespread allele-specific topological domains in the human genome are not confined to imprinted gene clusters.

Richer S, Tian Y, Schoenfelder S, Hurst L, Murrell A, Pisignano G Genome Biol. 2023; 24(1):40.

PMID: 36869353 PMC: 9983196. DOI: 10.1186/s13059-023-02876-2.

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