Epididymis-specific RNase A family genes regulate fertility and small RNA processing
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1166223 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30821206_1.fastq.gz | Fastqsanger.gz | |||
| SRR30821206_2.fastq.gz | Fastqsanger.gz | |||
| SRR30821207_1.fastq.gz | Fastqsanger.gz | |||
| SRR30821207_2.fastq.gz | Fastqsanger.gz | |||
| SRR30821208_1.fastq.gz | Fastqsanger.gz |
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Project description:Sperm small RNAs are implicated in intergenerational transmission of paternal environmental effects. Small RNAs generated by cleavage of tRNAs, known as tRNA fragments (tRFs) or tRNA-derived RNAs (tDRs or tsRNAs), are an abundant class of RNAs in mature sperm, and can be modulated by environmental conditions. The biogenesis of tRFs in the male reproductive tract remains poorly understood. Angiogenin, a member of the Ribonuclease A superfamily (RNase A), cleaves tRNAs to generate tRFs in response to cellular stress. Four paralogs of Angiogenin, namely Rnase9, Rnase10, Rnase11, and Rnase12, are specifically expressed in the epididymis —a long, convoluted tubule where sperm mature and acquire fertility and motility. The biological functions of these genes remain largely unknown. Here, by generating mice deleted for all four genes (Rnase9-12-/-, termed “KO” for Knock Out), we report that these genes regulate fertility and small RNA levels. KO mice showed complete male sterility. KO sperm fertilized oocytes in vitro but failed to efficiently fertilize oocytes in vivo due to an inability of sperm to pass through the utero-tubular junction. Intriguingly, there were decreased levels of fragments of tRNAs (tRFs) and rRNAs (rRNA-derived small RNAs or rsRNAs) in the KO epididymis and epididymal luminal fluid. RNases 9-12 did not show ribonucleolytic activity in-vitro, suggesting that the changes in tRF and rsRNA levels are independent of enzymatic activity of these proteins. Importantly, KO sperm showed a dramatic decrease in the levels of tRFs, demonstrating a role of epididymis-specific Rnase9-12 genes in regulating sperm small RNA composition. Together, our results reveal an unexpected role of four epididymis-specific non-canonical RNase A family genes in regulating fertility and small RNA processing.
2024-12-26 | GSE278291 | GEO
Project description:Sperm small RNAs are implicated in intergenerational transmission of paternal environmental effects. Small RNAs generated by the cleavage of tRNAs, known as tRNA fragments (tRFs) or tRNA-derived RNAs (tDRs or tsRNAs), are an abundant class of RNAs in mature sperm and can be modulated by environmental conditions. The biogenesis of tRFs in the male reproductive tract remains poorly understood. Angiogenin, a member of the ribonuclease A superfamily (RNase A), cleaves tRNAs to generate tRFs in response to cellular stress. Four paralogs of Angiogenin, namely Rnase9, Rnase10, Rnase11, and Rnase12, are specifically expressed in the epididymis-a long, convoluted tubule where sperm mature and acquire fertility and motility. Here, by generating mice deleted for all four genes (Rnase9-12-/-, termed "KO" for Knock Out), we report that these genes regulate fertility and small RNA levels. KO male mice are sterile; KO sperm fertilized oocytes in vitro but failed to efficiently fertilize oocytes in vivo due to an inability of sperm to pass through the utero-tubular junction. Intriguingly, there were decreased levels of tRFs and rRNAs (rRNA-derived small RNAs or rsRNAs) in the KO epididymis and epididymal luminal fluid, although RNases 9-12 did not show ribonucleolytic activity in vitro. Importantly, KO sperm showed a dramatic decrease in the levels of tRFs, demonstrating a role of epididymis-specific Rnase9-12 genes in regulating sperm small RNA composition. Together, our results reveal an unexpected role of four epididymis-specific noncanonical ribonuclease A family genes in regulating fertility and small RNA processing.
| S-EPMC11647505 | biostudies-literature
Project description:Sperm small RNAs are implicated in intergenerational transmission of paternal environmental effects. Small RNAs generated by cleavage of tRNAs, known as tRNA fragments (tRFs), are an abundant class of RNAs in mature sperm, and can be modulated by environmental conditions. The ribonuclease(s) responsible for the biogenesis of tRFs in the male reproductive tract remains unknown. Angiogenin, a member of the Ribonuclease A superfamily (RNase A), cleaves tRNAs to generate tRFs in response to cellular stress. Four paralogs of Angiogenin, namely Rnase9, Rnase10, Rnase11, and Rnase12, are specifically expressed in the epididymis-a long, convoluted tubule where sperm mature and acquire fertility and motility. The biological functions of these genes remain largely unknown. Here, by generating mice deleted for all four genes (Rnase9-12-/-, termed "KO" for Knock Out), we report that these genes regulate fertility and RNA processing. KO mice showed complete male sterility. KO sperm fertilized oocytes in vitro but failed to efficiently fertilize oocytes in vivo, likely due to an inability of sperm to pass through the utero-tubular junction. Intriguingly, there were decreased levels of fragments of tRNAs (tRFs) and rRNAs (rRNA-derived small RNAs or rsRNAs) in the KO epididymis and epididymal luminal fluid, implying that Rnase9-12 regulate the biogenesis and/or stability of tRFs and rsRNAs. Importantly, KO sperm showed a dramatic decrease in the levels of tRFs, demonstrating a role of Rnase9-12 in regulating sperm RNA composition. Together, our results reveal an unexpected role of four epididymis-specific non-canonical RNase A family genes in fertility and RNA processing.
| S-EPMC11383283 | biostudies-literature
Project description:Study question: Can region-specific transcriptional profiling of the epididymis from fertile and sub-fertile bulls predict the aetiology of fertility/subfertility in males? Summary answer:The highly regulated gene expression along the bovine epididymis is affected by the fertility status of bulls used for artificial insemination. What is known already: In mammals, sperm maturation and storage occur in the epididymis. Each epididymal segment has his own transcriptomic signature that modulates the intraluminal composition that governs sequential modifications of the maturing male gamete. Main results and the role of chance: Hierarchical clustering and Principal Component Analysis revealed a clear separation between caput, corpus and cauda epididymides. Some transcripts characterize a particular anatomical segment, whereas others are expressed in two out of three epididymal segments. GO analysis allowed deduction of specific functions played by each epididymal segment. The transcriptional profiles between fertile vs. sub-fertile conditions clustered most closely in the corpus and cauda segments, whereas the profiles in the caput segment were distinct between fertile and sub-fertile bulls. Of the differently expressed genes, ten (including AKAP4, SMCP, SPATA3, TCP11, ODF1, CTCFL, SPATA18, ADAM28, SORD and FAM161A) were found to exert functions related to reproductive systems and 5 genes (including DEAD, CYST11, DEFB119, DEFB124 and MX1) were found to be associated with the defence response. Limitations, reasons for caution: Further work is required to correlate these modulations of epididymal functions with sperm fertilizing ability in order to understand the aetiology of certain cases of idiopathic infertility in livestock and men. Wider implications of the findings: As fertility can be quantified in bulls used for artificial insemination, this species is a unique model to aid in the understanding of male fertility/subfertility in man.Our data provide a molecular characterization that will facilitate advances in understanding the involvement of epididymalphysiology in sub/infertility aetiology.
2017-03-31 | GSE96602 | GEO
Project description:SUBMITTER_CITATION: Dubé E and Cyr DG, The Blood-Epididymis and Human Male Fertility. In: Biology and Regulation of Blood-Tissue Barriers, Cheng CY Editor. 2010, Landes Bioscience. The epididymis can be subdivided into three regions, the caput, corpus and cauda epididymidis, that have different characteristics and functions. Goal was to determine the differential pattern of gene expression along the regions of the human epididymis.
2010-08-26 | GSE23812 | GEO
Project description:RNA processing and degradation is initiated by endonucleolytic cleavage of the target RNAs. In many bacteria, this activity is performed by RNase E which is not present in Bacillus subtilis and other Gram-positive bacteria. Recently, the essential endoribonuclease RNase Y has been discovered in B. subtilis. This RNase is involved in the degradation of bulk mRNA suggesting a major role in mRNA metabolism. However, only a few targets of RNase Y have been identified so far. In order to assess the global impact of RNase Y, we compared the transcriptomes of strains expressing RNase Y or depleted for RNase Y. Our results indicate that processing by RNase Y results in accumulation of about 80 mRNAs. Some of these targets were substantially stabilized by RNase Y depletion, resulting in half-lives in the range of an hour. Moreover, about 40 mRNAs were less abundant when RNase Y was depleted among them the mRNAs of the operons required for biofilm formation. Interestingly, overexpression of RNase Y was sufficient to induce biofilm formation. The results emphasize the importance of RNase Y for B. subtilis and are in support of the idea that RNase Y is the functional equivalent of RNase E.
2011-09-01 | GSE30430 | GEO
Project description:Mechanistic studies have revealed that TLR8 senses single-stranded RNA (ssRNA) fragments, processed via synergistic cleavage by ribonucleases (RNase) T2 and RNase A family members. Processing by these RNases releases uridines and purine-terminated residues resulting in TLR8 activation. Monocytes show high expression of RNase 6, yet this RNase has not been analyzed for its physiological contribution to recognition of bacterial RNA by TLR8. Herein, we characterized molecular RNase 6 cleavage mechanisms. BLaER1 RNASE6-/- cells showed a dampened TLR8-dependent response upon stimulation with isolated bacterial RNA (bRNA) but also upon infection with live whole bacteria. Pretreatment of bacterial RNA with recombinant RNase 6 generated fragments that induced stimulation in RNASE6 knockout cells. 2’O-RNA methyl modification, when introduced at the first uridine in the UA dinucleotide, impaired upstream processing by RNase 6 and dampened TLR8 stimulation. In summary, this data shows that RNase 6 plays a critical role in the processing of bacterial RNA by generating uridine-terminated breakdown products that ultimately activate TLR8.
2024-09-12 | PXD053881 | Pride
Project description:RNA processing and degradation is initiated by endonucleolytic cleavage of the target RNAs. In many bacteria, this activity is performed by RNase E which is not present in Bacillus subtilis and other Gram-positive bacteria. Recently, the essential endoribonuclease RNase Y has been discovered in B. subtilis. This RNase is involved in the degradation of bulk mRNA suggesting a major role in mRNA metabolism. However, only a few targets of RNase Y have been identified so far. In order to assess the global impact of RNase Y, we compared the transcriptomes of strains expressing RNase Y or depleted for RNase Y. Our results indicate that processing by RNase Y results in accumulation of about 80 mRNAs. Some of these targets were substantially stabilized by RNase Y depletion, resulting in half-lives in the range of an hour. Moreover, about 40 mRNAs were less abundant when RNase Y was depleted among them the mRNAs of the operons required for biofilm formation. Interestingly, overexpression of RNase Y was sufficient to induce biofilm formation. The results emphasize the importance of RNase Y for B. subtilis and are in support of the idea that RNase Y is the functional equivalent of RNase E. To study the global function of RNase Y, a microarray analysis was performed with a B. subtilis strain allowing controlled depletion of RNase Y. Strain GP193 (Commichau et al., 2009, Mol. Cell. Proteomics 8: 1350-1360) expressing the rny gene under the control of a xylose-inducible promoter was cultivated in CSE minimal medium in the presence or absence of the inducer xylose. The transcriptomes of the two cultures (i.e. expressing RNase Y and depleted for RNase Y) were compared at a timepoint at which the reduced RNase Y amounts already affected the mRNA turnover whereas the growth rates of the two cultures were still almost identical.
2011-08-31 | E-GEOD-30430 | biostudies-arrayexpress
Project description:The epithelium lining the epididymis in the male reproductive tract maintains a luminal environment that promotes sperm cell maturation. This process is dependent on the coordinated expression of many genes that encode proteins with a role in epithelial transport. We previously generated genome-wide maps of open chromatin in primary human fetal epididymis epithelial cells to identify potential regulatory elements controlling coordinated gene expression in the epididymis epithelium. Subsequent in silico analysis identified transcription factor binding sites (TFBS) that were over-represented in the HEE open chromatin, include the motif for paired box 2 (PAX2). PAX2 is a critical transcriptional regulator of urogenital tract development, which is well studied in the kidney but is unexplored in the epididymis. Due to the limited lifespan of primary HEE cells in culture we investigated the role of PAX2 in an immortalized HEE cell line (REP). First, REP cells were evaluated by DNase-seq and their open chromatin map overlapped that of primary HEE cells at ~ 65% of sites. Moreover, the PAX2-binding motif was again identified as an overrepresented TFBS within intergenic open chromatin, though on fewer chromosomes than in the primary HEE cells. To identify PAX2-target genes in REP cells, RNA-seq analysis was performed after siRNA-mediated depletion of PAX2 in comparison to a non-targeting siRNA. In response to PAX2-represssion, 3142 transcripts were differentially expressed (1334 up-regulated and 1808 down-regulated). Novel PAX2 targets included multiple genes encoding proteins with a predicted function in the epididymis epithelium. mRNA profile of control and PAX2 knockdown REP cells
2015-01-07 | E-GEOD-59781 | biostudies-arrayexpress
Project description:The epithelium lining the epididymis in the male reproductive tract maintains a luminal environment that promotes sperm cell maturation. This process is dependent on the coordinated expression of many genes that encode proteins with a role in epithelial transport. We previously generated genome-wide maps of open chromatin in primary human fetal epididymis epithelial cells to identify potential regulatory elements controlling coordinated gene expression in the epididymis epithelium. Subsequent in silico analysis identified transcription factor binding sites (TFBS) that were over-represented in the HEE open chromatin, include the motif for paired box 2 (PAX2). PAX2 is a critical transcriptional regulator of urogenital tract development, which is well studied in the kidney but is unexplored in the epididymis. Due to the limited lifespan of primary HEE cells in culture we investigated the role of PAX2 in an immortalized HEE cell line (REP). First, REP cells were evaluated by DNase-seq and their open chromatin map overlapped that of primary HEE cells at ~ 65% of sites. Moreover, the PAX2-binding motif was again identified as an overrepresented TFBS within intergenic open chromatin, though on fewer chromosomes than in the primary HEE cells. To identify PAX2-target genes in REP cells, RNA-seq analysis was performed after siRNA-mediated depletion of PAX2 in comparison to a non-targeting siRNA. In response to PAX2-represssion, 3142 transcripts were differentially expressed (1334 up-regulated and 1808 down-regulated). Novel PAX2 targets included multiple genes encoding proteins with a predicted function in the epididymis epithelium.
2015-01-07 | GSE59781 | GEO