International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 84 - WHAT IS THE ROLE OF NESPAS, A GENE THAT RUNS ANTISENSE TO NESP AND GENERATES A MULTITUDE OF IMPRINTED TRANSCRIPTS?

J Peters
MRC Mammalian Genetics Unit
Harwell
Didcot
Oxon OX11 0RD

Co-Authors: 3)Peters J, 3)Ball ST, 3)Skinner JA, 3)Nottingham W, 1)Plagge A, 1)Kelsey G, 2)Hayes C, Hacker T and Williamson CM
Institutions: 3)MRC Mammalian Genetics Unit, 1)The Babraham Institute, 2) Current address Merck, Sharp and Dohme,

Within the imprinted Gnas complex in distal mouse chromosome 2 there is a gene called Nesp transcribed in the sense direction.  Nesp has maternal specific expression. Several antisense RNAs, all of which are imprinted, paternally expressed, and non-coding, overlap the Nesp exons. These antisense RNAs are called Nespas. In addition to an unspliced form, there are five alternatively spliced forms that are up to 1.4kb in length. The splice variants, and probably the unspliced form as well, start approximately 13 kb downstream of Nesp in a region of maternal methylation .

An increasing number of imprinted genes have antisense transcripts associated with them. One of the issues in imprinting is to define their role. One thought is that they may function as cis-acting regulators of the sense gene they overlap, and another is that they are spurious transcripts with no role of their own.  In newborn heart Nesp is maternally expressed and Nespas is paternally expressed, which would be consistent with the idea that the antisense controls expression of the sense transcript. However, although Nesp and Nespas are also expressed from opposite parental alleles in mid gestation embryos, Nesp expression is primarily seen in the somites and developing vasculature whereas Nespas is mainly detected in the developing limb, particularly in the progress zone. These observations suggest that Nespas may not be involved in regulating the imprinting of Nesp and that it has an alternative role. In order to explore the role of Nespas further, a gene knock-out experiment is underway.


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