Abstract
MicroRNA (miRNA), a small non-coding RNA that functions as a mediator in gene silencing, plays important roles in gene regulation in various vital functions and activities. Here we show that the miR-29 members are upregulated in klotho-deficient [klotho(−/−)] mice, a senescence-model animal, and also in normal elderly ICR mice relative to wild-type littermates and young ICR mice. In addition, levels of type IV collagen, a major component of basement membranes and a putative target of miR-29, were lower in klotho(−/−) and elderly ICR mice than in wild-type littermates and young ICR mice. RNA degradation mediated by miR-29 may participate in the suppression of type IV collagen, both in vivo and in vitro. Taken together, our current findings suggest that the miR-29 upregulated in aging may be involved in the downregulation of type IV collagen, leading to a possible weakening of the basal membrane in senescent tissues, and miR-29 may be a useful molecular marker of senescence.
Highlights
Senescence is a set of biological changes that occurs in an individual with increasing age
Hundreds of miRNA genes have been found in animals and plants [see the microRNA database: http://www.mirbase. org/index.shtml]. miRNAs play essential roles in gene regulation by inhibiting translation of messenger RNAs that are partially complementary to the miRNAs, and by digestion of mRNAs that are nearly complementary to the miRNAs, or by RNA interference (RNAi), during cell proliferation, differentiation and development [1,2,3,4,5]
It has been found that a major small RNA class transition from retrotransposon-derived small interfering RNAs and Piwi-interacting RNAs to zygotically expressed miRNAs occurs during early development of preimplantation embryos [6], and tissue- or organ-specific expression patterns of miRNAs are generated thereafter [4,7,8,9]
Summary
Senescence is a set of biological changes that occurs in an individual with increasing age. In order to understand such complex senescent phenomena at a molecular level, finding biological molecules that show quantitative and qualitative variation with increasing age is vital; and such molecules may be useful as senescence makers. MiRNAs play essential roles in gene regulation by inhibiting translation of messenger RNAs (mRNAs) that are partially complementary to the miRNAs, and by digestion of mRNAs that are nearly complementary to the miRNAs, or by RNA interference (RNAi), during cell proliferation, differentiation and development [1,2,3,4,5]. Expression profiles of miRNAs are quite useful in understanding complex gene regulation involving miRNAs and in characterizing miRNAs themselves. It has been found that a major small RNA class transition from retrotransposon-derived small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs) to zygotically expressed miRNAs occurs during early development of preimplantation embryos [6], and tissue- or organ-specific expression patterns of miRNAs are generated thereafter [4,7,8,9]
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