Piwi-like RNA-mediated gene silencing 1 [Mus musculus (house mouse)]

Reviewed functional gene

1. Abstract
The piwi family genes are crucial for stem cell self-renewal, RNA silencing, and translational regulation in diverse organisms. However, their function in mammals remains unexplored. Here we report the cloning of a ... The piwi family genes are crucial for stem cell self-renewal, RNA silencing, and translational regulation in diverse organisms. However, their function in mammals remains unexplored. Here we report the cloning of a murine piwi gene (miwi) essential for spermatogenesis. miwi encodes a cytoplasmic protein specifically expressed in spermatocytes and spermatids. miwi(null) mice display spermatogenic arrest at the beginning of the round spermatid stage, resembling the phenotype of CREM, a master regulator of spermiogenesis. Furthermore, mRNAs of ACT (activator of CREM in testis) and CREM target genes are downregulated in miwi(null) testes. Whereas MIWI and CREM do not regulate each other's expression, MIWI complexes with mRNAs of ACT and CREM target genes. Hence, MIWI may control spermiogenesis by regulating the stability of these mRNAs. PMID: [12062093]  

2. Abstract
Small RNAs associate with Argonaute proteins and serve as sequence-specific guides to regulate messenger RNA stability, protein synthesis, chromatin organization and genome structure. In animals, Argonaute proteins segregate into two subfamilies. The ... Small RNAs associate with Argonaute proteins and serve as sequence-specific guides to regulate messenger RNA stability, protein synthesis, chromatin organization and genome structure. In animals, Argonaute proteins segregate into two subfamilies. The Argonaute subfamily acts in RNA interference and in microRNA-mediated gene regulation using 21-22-nucleotide RNAs as guides. The Piwi subfamily is involved in germline-specific events such as germline stem cell maintenance and meiosis. However, neither the biochemical function of Piwi proteins nor the nature of their small RNA guides is known. Here we show that MIWI, a murine Piwi protein, binds a previously uncharacterized class of approximately 29-30-nucleotide RNAs that are highly abundant in testes. We have therefore named these Piwi-interacting RNAs (piRNAs). piRNAs show distinctive localization patterns in the genome, being predominantly grouped into 20-90-kilobase clusters, wherein long stretches of small RNAs are derived from only one strand. Similar piRNAs are also found in human and rat, with major clusters occurring in syntenic locations. Although their function must still be resolved, the abundance of piRNAs in germline cells and the male sterility of Miwi mutants suggest a role in gametogenesis. PMID: [16751776]  

3. Abstract
Small RNAs bound to Argonaute proteins recognize partially or fully complementary nucleic acid targets in diverse gene-silencing processes. A subgroup of the Argonaute proteins--known as the 'Piwi family'--is required for germ- and ... Small RNAs bound to Argonaute proteins recognize partially or fully complementary nucleic acid targets in diverse gene-silencing processes. A subgroup of the Argonaute proteins--known as the 'Piwi family'--is required for germ- and stem-cell development in invertebrates, and two Piwi members--MILI and MIWI--are essential for spermatogenesis in mouse. Here we describe a new class of small RNAs that bind to MILI in mouse male germ cells, where they accumulate at the onset of meiosis. The sequences of the over 1,000 identified unique molecules share a strong preference for a 5' uridine, but otherwise cannot be readily classified into sequence families. Genomic mapping of these small RNAs reveals a limited number of clusters, suggesting that these RNAs are processed from long primary transcripts. The small RNAs are 26-31 nucleotides (nt) in length--clearly distinct from the 21-23 nt of microRNAs (miRNAs) or short interfering RNAs (siRNAs)--and we refer to them as 'Piwi-interacting RNAs' or piRNAs. Orthologous human chromosomal regions also give rise to small RNAs with the characteristics of piRNAs, but the cloned sequences are distinct. The identification of this new class of small RNAs provides an important starting point to determine the molecular function of Piwi proteins in mammalian spermatogenesis. PMID: [16751777]  

4. Abstract
Noncoding small RNAs have emerged as important regulators of gene expression at both transcriptional and posttranscriptional levels. Particularly, microRNA (miRNA)-mediated translational repression involving PIWI/Argonaute family proteins has been widely recognized as a ... Noncoding small RNAs have emerged as important regulators of gene expression at both transcriptional and posttranscriptional levels. Particularly, microRNA (miRNA)-mediated translational repression involving PIWI/Argonaute family proteins has been widely recognized as a novel mechanism of gene regulation. We previously reported that MIWI, a murine PIWI family member, is required for initiating spermiogenesis, a process that transforms round spermatids into mature sperm. MIWI is a cytoplasmic protein present in spermatocytes and round spermatids, and it is required for the expression of its target mRNAs involved in spermiogenesis. Most recently, we discovered a class of noncoding small RNAs called PIWI-interacting RNAs (piRNAs) that are abundantly expressed during spermiogenesis in a MIWI-dependent fashion. Here, we show that MIWI associates with both piRNAs and mRNAs in cytosolic ribonucleoprotein and polysomal fractions. As polysomes increase in early spermiogenesis, MIWI increases in polysome fractions. Moreover, MIWI associates with the mRNA cap-binding complex. Interestingly, MIWI is required for the expression of not only piRNAs but also a subset of miRNAs, despite the presence of Dicer. These results suggest that MIWI has a complicated role in the biogenesis and/or maintenance of two distinct types of small RNAs. Together, our results indicate that MIWI, a PIWI subfamily protein, uses piRNA as the major, but not exclusive, binding partner, and it is associated with translational machinery. PMID: [16938833]  

5. Abstract
The mouse Piwi family proteins (MILI, MIWI and MIWI2) play pivotal roles in spermatogenesis through transcriptional and post-transcriptional gene regulation. To reveal the molecular functions of these proteins, we investigate the ... The mouse Piwi family proteins (MILI, MIWI and MIWI2) play pivotal roles in spermatogenesis through transcriptional and post-transcriptional gene regulation. To reveal the molecular functions of these proteins, we investigate the proteins that bind to MILI in adult mouse testes. We found that both MILI and MIWI bind to TDRD1/MTR-1, which is also an essential protein for spermatogenesis. Co-immunoprecipitation assays and subcellular localization of the proteins and mutants thereof revealed a complex formation involving MILI, MIWI and TDRD1/MTR-1. In addition, the subcellular localizations of MILI and TDRD1/MTR-1 were altered, and chromatoid body formation was impaired in the MIWI-null round spermatids. These data suggest that the formation of complexes between MILI, MIWI and TDRD1/MTR-1 is critical for the integrated subcellular localizations of these proteins, and is presumably essential for spermatogenesis. PMID: [19735482]  

6. Abstract
PIWI proteins and piRNAs have been linked to transposon silencing in the primordial mouse testis, but their function in the adult testis remains elusive. Here we report the cytological characterization of piRNAs ... PIWI proteins and piRNAs have been linked to transposon silencing in the primordial mouse testis, but their function in the adult testis remains elusive. Here we report the cytological characterization of piRNAs in the adult mouse testis and the phenotypic analysis of Miwi(-/-); Mili(-/-) mice. We show that piRNAs are specifically present in germ cells, especially abundant in spermatocytes and early round spermatids, regardless of the type of the genomic sequences to which they correspond. piRNAs and PIWI proteins are present in both the cytoplasm and nucleus. In the cytoplasm, they are enriched in the chromatoid body; whereas in the nucleus they are enriched in the dense body, a male-specific organelle associated with synapsis and the formation of the XY body during meiosis. Moreover, by generating Miwi(-/-); Mili(-/-) mice, which lack all PIWI proteins in the adult, we show that PIWI proteins and presumably piRNAs in the adult are required only for spermatogenesis. Spermatocytes without PIWI proteins are arrested at the pachytene stage, when the sex chromosomes undergo transcriptional silencing to form the XY body. These results pinpoint a function of the PIWI protein subfamily to meiosis during spermatogenesis. PMID: [21539824]  

1000G (Phase 3): 1090   ESP6500 (SI-V2): 159   ExAC (r0.3.1): 772   dbSNP(Build 147): 2697

Chinese health control (254): 12  European health control (283): 4   Chinese patients (168):  

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