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[小鼠中的表观遗传遗传:RNA和微小RNA的参与。]

[Epigenetic heredity in mice: involvement of RNA and miRNas.].

作者信息

Rassoulzadegan Minoo, Grandjean Valérie, Gounon Pierre, Cuzin François

机构信息

Unité 636 de l'Inserm et Université de Nice-Sophia Antipolis, 06108 Nice cedex, France Equipe labellisée Ligue Nationale Française Contre le Cancer.

出版信息

J Soc Biol. 2007;201(4):397-9. doi: 10.1051/jbio:2007911. Epub 2008 Mar 5.

Abstract

By contrast with a wide definition of the 'epigenetic variation', including all changes in gene expression that do not result from alteration of the gene structure, a more restricted class had been defined, initially in plants, under the name 'paramutation'. It corresponds to epigenetic modifications distinct from the regulatory interactions of the cell differentiation pathways, mitotically stable and sexually transmitted with non-Mendelian patterns. This class of epigenetic changes appeared for some time restricted to the plant world, but examples progressively accumulated of epigenetic inheritance in organisms ranging from mice to humans. Occurrence of paramutation in the mouse and possible mechanisms were then established in the paradigmatic case of a mutant phenotype maintained and hereditarily transmitted by wild type homozygotes. Together with recent findings in plants indicative of a necessary step of RNA amplification in the reference maize paramutation, the mouse studies point to a new role of RNA, as an inducer and hereditary determinant of epigenetic variation. Given the known presence of a wide range of RNAs in human spermatozoa, as well as a number of unexplained cases of familial disease predisposition and transgenerational maintenance, speculations can be extended to possible roles of RNA-mediated inheritance in human biology and pathology.

摘要

与“表观遗传变异”的宽泛定义相反,“表观遗传变异”包括所有并非由基因结构改变引起的基因表达变化,最初在植物中定义了一个更为狭义的类别,名为“副突变”。它对应于与细胞分化途径的调控相互作用不同的表观遗传修饰,这种修饰在有丝分裂过程中稳定且以非孟德尔模式进行有性传递。这类表观遗传变化曾一度似乎仅限于植物界,但从小鼠到人类等生物体中表观遗传遗传的例子逐渐增多。随后,在野生型纯合子维持并遗传传递突变表型的典型案例中,确定了小鼠中副突变的发生及其可能机制。结合植物方面的最新发现,即在参考玉米副突变中表明RNA扩增是一个必要步骤,小鼠研究指出了RNA作为表观遗传变异的诱导物和遗传决定因素的新作用。鉴于已知人类精子中存在多种RNA,以及一些无法解释的家族性疾病易感性和跨代维持病例,人们可以推测RNA介导的遗传在人类生物学和病理学中的可能作用。

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