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端粒维持和端粒酶活性在无性和有性蠕虫中受到不同的调节。

Telomere maintenance and telomerase activity are differentially regulated in asexual and sexual worms.

机构信息

Centre for Genetics and Genomics and Children's Brain Tumour Research Centre, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.

出版信息

Proc Natl Acad Sci U S A. 2012 Mar 13;109(11):4209-14. doi: 10.1073/pnas.1118885109. Epub 2012 Feb 27.

Abstract

In most sexually reproducing animals, replication and maintenance of telomeres occurs in the germ line and during early development in embryogenesis through the use of telomerase. Somatic cells generally do not maintain telomere sequences, and these cells become senescent in adults as telomeres shorten to a critical length. Some animals reproduce clonally and must therefore require adult somatic mechanisms for maintaining their chromosome ends. Here we study the telomere biology of planarian flatworms with apparently limitless regenerative capacity fueled by a population of highly proliferative adult stem cells. We show that somatic telomere maintenance is different in asexual and sexual animals. Asexual animals maintain telomere length somatically during reproduction by fission or when regeneration is induced by amputation, whereas sexual animals only achieve telomere elongation through sexual reproduction. We demonstrate that this difference is reflected in the expression and alternate splicing of the protein subunit of the telomerase enzyme. Asexual adult planarian stem cells appear to maintain telomere length over evolutionary timescales without passage through a germ-line stage. The adaptations we observe demonstrate indefinite somatic telomerase activity in proliferating stem cells during regeneration or reproduction by fission, and establish planarians as a pertinent model for studying telomere structure, function, and maintenance.

摘要

在大多数有性繁殖的动物中,端粒的复制和维持发生在生殖细胞中,并在胚胎发生的早期发育中通过端粒酶来完成。体细胞通常不维持端粒序列,这些细胞在成年时会因为端粒缩短到临界长度而衰老。一些动物进行无性繁殖,因此必须依赖成年体细胞机制来维持染色体末端。在这里,我们研究了具有明显无限再生能力的扁形动物(例如涡虫)的端粒生物学,这种再生能力是由一群高度增殖的成年干细胞提供的。我们发现,无性繁殖和有性繁殖的动物的体细胞端粒维持方式不同。无性繁殖的动物在分裂生殖或通过截肢诱导再生时,通过分裂生殖在体细胞中维持端粒长度,而有性繁殖的动物仅通过有性繁殖才能实现端粒延长。我们证明,这种差异反映在端粒酶蛋白亚基的表达和可变剪接中。无性繁殖的成年涡虫干细胞似乎在进化时间尺度内维持端粒长度,而无需经过生殖细胞阶段。我们观察到的这些适应表明,在通过分裂生殖进行再生或繁殖时,增殖干细胞中存在无限的端粒酶活性,并确立了扁形动物作为研究端粒结构、功能和维持的相关模型。

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本文引用的文献

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Telomerase deficiency in a colonial ascidian after prolonged asexual propagation.长期无性繁殖后,群体海鞘中端粒酶缺乏。
J Exp Zool B Mol Dev Evol. 2011 Jun 15;316(4):276-83. doi: 10.1002/jez.b.21399. Epub 2011 Jan 11.
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Potential for clonal animals in longevity and ageing studies.克隆动物在长寿和衰老研究中的潜力。
Biogerontology. 2011 Oct;12(5):387-96. doi: 10.1007/s10522-011-9333-8. Epub 2011 Apr 9.
3
Planarian stem cells: a simple paradigm for regeneration.涡虫干细胞:再生的简单范例。
Trends Cell Biol. 2011 May;21(5):304-11. doi: 10.1016/j.tcb.2011.01.005. Epub 2011 Feb 25.
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The role of telomeres and telomerase in stem cell aging.端粒和端粒酶在干细胞衰老中的作用。
FEBS Lett. 2010 Sep 10;584(17):3826-30. doi: 10.1016/j.febslet.2010.07.042. Epub 2010 Aug 3.
6
Telomere biology in Metazoa.后生动物中的端粒体生物学。
FEBS Lett. 2010 Sep 10;584(17):3741-51. doi: 10.1016/j.febslet.2010.07.031. Epub 2010 Jul 23.
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Telomeres: protecting chromosomes against genome instability.端粒:保护染色体免受基因组不稳定的影响。
Nat Rev Mol Cell Biol. 2010 Mar;11(3):171-81. doi: 10.1038/nrm2848. Epub 2010 Feb 3.

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