Systematic variation in mRNA 3′-processing signals during mouse spermatogenesis

Liu, Donglin; Brockman, J. Michael; Dass, Brinda; Hutchins, Lucie N.; Singh, Priyam; McCarrey, John R.; MacDonald, Clinton C.; Graber, Joel H.

doi:10.1093/nar/gkl919

Cited by 120 publications

(151 citation statements)

References 87 publications

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“…Although polyadenylation is nearly universal, features of polyadenylation are different in mammalian male germ cells than in other tissues: male germ cell mRNAs exhibit increased alternative polyadenylation (3,4), decreased use of the AAUAAA polyadenylation signal (5,6), and reduced dependence on downstream sequence elements (DSEs) (7). These differences suggest a modified mechanism for polyadenylation in male germ cells.…”

mentioning

confidence: 99%

Loss of polyadenylation protein τCstF-64 causes spermatogenic defects and male infertility

Dass

Tardif

Park

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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131

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Polyadenylation, the process of eukaryotic mRNA 3 end formation, is essential for gene expression and cell viability. Polyadenylation of male germ cell mRNAs is unusual, exhibiting increased alternative polyadenylation, decreased AAUAAA polyadenylation signal use, and reduced downstream sequence element dependence. CstF-64, the RNA-binding component of the cleavage stimulation factor (CstF), interacts with pre-mRNAs at sequences downstream of the cleavage site. In mammalian testes, meiotic XY-body formation causes suppression of X-linked CstF-64 expression during pachynema. Consequently, an autosomal paralog, CstF-64 (gene name Cstf2t), is expressed during meiosis and subsequent haploid differentiation. Here we show that targeted disruption of Cstf2t in mice causes aberrant spermatogenesis, specifically disrupting meiotic and postmeiotic development, resulting in male infertility resembling oligoasthenoteratozoospermia. Furthermore, the Cstf2t mutant phenotype displays variable expressivity such that spermatozoa show a broad range of defects. The overall phenotype is consistent with a requirement for CstF-64 in spermatogenesis as indicated by the significant changes in expression of thousands of genes in testes of Cstf2t ؊/؊ mice as measured by microarray. Our results indicate that, although the infertility in Cstf2t ؊/؊ males is due to low sperm count, multiple genes controlling many aspects of germ-cell development depend on CstF-64 for their normal expression. Finally, these transgenic mice provide a model for the study of polyadenylation in an isolated in vivo system and highlight the role of a growing family of testis-expressed autosomal retroposed variants of X-linked genes.spermatogenesis ͉ oligoasthenoteratozoospemia ͉ meiosis ͉ XY body ͉ meiotic sex chromosome inactivation P olyadenylation, the process of mRNA 3Ј end formation, is required for the synthesis, transport, translation, and stability of eukaryotic mRNAs (1, 2). Although polyadenylation is nearly universal, features of polyadenylation are different in mammalian male germ cells than in other tissues: male germ cell mRNAs exhibit increased alternative polyadenylation (3, 4), decreased use of the AAUAAA polyadenylation signal (5, 6), and reduced dependence on downstream sequence elements (DSEs) (7). These differences suggest a modified mechanism for polyadenylation in male germ cells.While examining these differences, we discovered CstF-64 (8), which is a paralog of the 64,000 M r subunit of the cleavage stimulation factor (CstF-64) (9-11). CstF-64 is expressed in nuclei of early spermatogenic cells (5, 12). However, because it is on the X chromosome, CstF-64 expression halts in pachytene spermatocytes because of meiotic sex chromosome inactivation (MSCI) (13). In contrast, CstF-64 expression begins in pachytene spermatocytes and continues in spermatocytes and early spermatids (refs. 5 and 12; summarized in Fig. 1). CstF-64 is the only known CstF-64 homolog expressed during male meiosis, thus making it a candidate to play a critical role in sper...

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mentioning

confidence: 99%

Loss of polyadenylation protein τCstF-64 causes spermatogenic defects and male infertility

Dass

Tardif

Park

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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131

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“…It is particularly useful to detect RNA isoforms of the same gene, yet, with a relatively strong background noise and vector contamination issue. Liu et al (2007) built EST libraries from primitive type A spermatogonia, pachytene spermatocytes, round spermatids, and Sertoli cells of mice, and focused on the 3 0 -UTR of the transcripts. They found that even for the same transcript, the 3 0 -UTR location and length varied at different stages in spermatogenesis.…”

Section: R135mentioning

confidence: 99%

Long noncoding RNAs in spermatogenesis: insights from recent high-throughput transcriptome studies

Luk¹,

Chan²,

Rennert³

et al. 2014

Reproduction

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Spermatogenesis is a complex developmental process in which undifferentiated spermatogonia are differentiated into spermatocytes and spermatids through two rounds of meiotic division and finally giving rise to mature spermatozoa (sperm). These processes involve many testis-or male germ cell-specific gene products that undergo strict developmental regulations. As a result, identifying critical, regulatory genes controlling spermatogenesis provide the clues not only to the regulatory mechanism of spermatogenesis at the molecular level, but also to the identification of candidate genes for infertility or contraceptives development. Despite the biological importance in male germ cell development, the underlying mechanisms of stage-specific gene regulation and cellular transition during spermatogenesis remain largely elusive. Previous genomic studies on transcriptome profiling were largely limited to protein-coding genes. Importantly, protein-coding genes only account for a small percentage of transcriptome; the majority are noncoding transcripts that do not translate into proteins. Although small noncoding RNAs (ncRNAs) such as microRNAs, siRNAs, and Piwi-interacting RNAs are extensively investigated in male germ cell development, the role of long ncRNAs (lncRNAs), commonly defined as ncRNAs longer than 200 bp, is relatively unexplored. Herein, we summarize recent transcriptome studies on spermatogenesis and show examples that a subset of noncoding transcript population, known as lncRNAs, constitutes a novel regulatory target in spermatogenesis.

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“…Studies using expressed sequence tag (EST) data have revealed a tissue bias in poly(A) site usage. For example, mRNAs in the brain tend to have longer 3 0 UTRs while testes maintain shorter 3 0 UTRs as a result of poly(A) sites that are not frequently used in other tissue types (58,59).…”

Section: Mrnamentioning

confidence: 99%

miRNAs in cardiac disease: Sitting duck or moving target?

2012

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SummaryEmerging findings indicate that cells can produce both micro (mi)RNAs and their messenger (m)RNA targets in multiple processing variants in a tissue-and developmental stage-selective manner. Specifically, we find that cells accumulate a greater range of functional miRNAs than hitherto expected, whereas mRNAs with alternative 3 0 untranslated regions that include varying numbers of miRNA target sites are also seen to be common. This has important implications for both our understanding of miRNA function in a given biological context and the design of successful strategies for experimental or therapeutic intervention. In this review, we relate these new phenomena to miRNAs in the heart, where they are known to play critical roles during normal function as well as in cardiac disease. IUBMBIUBMB Life, 64(11): 872-878, 2012 Keywords cardiac disease; miRNA biogenesis; miRNA-target interaction; 3 0 untranslated region; mRNA 3 0 end cleavage; polyadenylation.

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Systematic variation in mRNA 3′-processing signals during mouse spermatogenesis

Cited by 120 publications

References 87 publications

Loss of polyadenylation protein τCstF-64 causes spermatogenic defects and male infertility

Loss of polyadenylation protein τCstF-64 causes spermatogenic defects and male infertility

Long noncoding RNAs in spermatogenesis: insights from recent high-throughput transcriptome studies

miRNAs in cardiac disease: Sitting duck or moving target?

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