pnldc1

PIWI-interacting RNAs (piRNAs) play critical and conserved roles in transposon silencing and gene regulation in the animal germline. Two distinct piRNA populations are present during mouse spermatogenesis: pre-pachytene piRNAs in fetal/neonatal testes and pachytene piRNAs in adult testes. PNLDC1 is required for both pre-pachytene piRNA and pachytene piRNA 3' end maturation in multiple species. However, whether PNLDC1 is the bona fide piRNA trimmer and the physiological role of 3' trimming of two distinct piRNA populations in spermatogenesis remain unclear...

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Learning points for clinicians PARN-like ribonuclease domain-containing exonuclease 1 (PNLDC1) forms a trimmer of piRNAs mediating 3'-splicing and plays an important role in meiosis and spermatogenesis. Here, we identified a novel nonsense PNLDC1 variant in a patient with Oligo-astheno-teratozoospermia (OAT) and poor clinical outcomes of intracytoplasmic sperm injection (ICSI) from a consanguineous Chinese family.

Male infertility is a major reproductive disorder, which is clinically characterized by highly heterogeneous phenotypes of abnormal sperm count or quality. To date, five male patients with biallelic loss-of-function (LOF) variants of PARN-like ribonuclease domain-containing exonuclease 1 (PNLDC1) have been reported to experience infertility with nonobstructive azoospermia. The aim of this study was to identify the genetic cause of male infertility with oligo-astheno-teratozoospermia (OAT) in a patient from a Chinese Han family...

 : In germ cells, small non-coding PIWI-interacting RNAs (piRNAs) work to silence harmful transposons to maintain genomic stability and regulate gene expression to ensure fertility. However, these piRNAs must undergo a series of steps during biogenesis to be properly loaded onto PIWI proteins and reach the correct nucleotide length. This review is focused on what we are learning about a crucial step in this process, piRNA trimming, in which pre-piRNAs are shortened to final lengths of 21-35 nucleotides. Recently, the 3'-5' exonuclease trimmer has been identified in various models as PNLDC1/PARN-1...

BACKGROUND: Ovarian cancer (OC) is the deadliest tumor in the female reproductive tract. And increased resistance to platinum-based chemotherapy represents the major obstacle in the treatment of OC currently. Robust and accurate gene expression models are crucial tools in distinguishing platinum therapy response and evaluating the prognosis of OC patients. METHODS: In this study, 230 samples from The Cancer Genome Atlas (TCGA) OV dataset were subjected to mRNA expression profiling, single nucleotide polymorphism (SNP), and copy number variation (CNV) analysis comprehensively to screen out the differentially expressed genes (DEGs)...

BACKGROUND: RNA binding proteins (RBPs) play an important role in a variety of cancers. However, their mechanisms in cancer progression are still limited especially in colorectal adenocarcinoma (COAD). Integrated analysis of RBPs will provide a better understanding of disease genesis and new insights into COAD treatment. METHODS: The gene expression data and corresponding clinical information for COAD were downloaded from The Cancer Genome Atlas (TCGA) database...

BACKGROUND: P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are short (21 to 35 nucleotides in length) and noncoding and are found almost exclusively in germ cells, where they regulate aberrant expression of transposable elements and postmeiotic gene expression. Critical to the processing of piRNAs is the protein poly(A)-specific RNase-like domain containing 1 (PNLDC1), which trims their 3' ends and, when disrupted in mice, causes azoospermia and male infertility. METHODS: We performed exome sequencing on DNA samples from 924 men who had received a diagnosis of nonobstructive azoospermia...

BACKGROUND: Colorectal cancer (CRC) is a kind of gastrointestinal tumor with serious high morbidity and mortality. Several reports have implicated the disorder of RNA-binding proteins (RBPs) in plenty of tumors, associating it to tumorigenesis and disease progression. The study is intended to construct novel prognostic biomarkers associated with CRC patients. METHODS: Data of gene expression was acquired from the TCGA database, prognosis-related genes were selected...

Colorectal cancer (CRC) is one of the most prevalent and fatal malignancies, and novel biomarkers for the diagnosis and prognosis of CRC must be identified. RNA-binding proteins (RBPs) are essential modulators of transcription and translation. They are frequently dysregulated in various cancers and are related to tumorigenesis and development. The mechanisms by which RBPs regulate CRC progression are poorly understood and no clinical prognostic model using RBPs has been reported in CRC. We sought to identify the hub prognosis-related RBPs and to construct a prognostic model for clinical use...

P-element induced wimpy testis (PIWIs) are crucial guardians of genome integrity, particularly in germ cells. While mammalian PIWIs have been primarily studied in mouse and rat, a homologue for the human PIWIL3 gene is absent in the Muridae family, and hence the unique function of PIWIL3 in germ cells cannot be effectively modeled by mouse knockouts. Herein, we investigated the expression, distribution, and interaction of PIWIL3 in bovine oocytes. We localized PIWIL3 to mitochondria, and demonstrated that PIWIL3 expression is stringently controlled both spatially and temporally before and after fertilization...

PIWI-interacting RNAs (piRNAs) of between approximately 24 and 31 nucleotides in length guide PIWI proteins to silence transposons in animal gonads, thereby ensuring fertility1 . In the biogenesis of piRNAs, PIWI proteins are first loaded with 5'-monophosphorylated RNA fragments called pre-pre-piRNAs, which then undergo endonucleolytic cleavage to produce pre-piRNAs1,2 . Subsequently, the 3'-ends of pre-piRNAs are trimmed by the exonuclease Trimmer (PNLDC1 in mouse)3-6 and 2'-O-methylated by the methyltransferase Hen1 (HENMT1 in mouse)7-9 , generating mature piRNAs...

PIWI-interacting RNAs (piRNAs) are small regulatory RNAs that bind to PIWI proteins to control transposons and maintain genome integrity in animal germ lines. piRNA 3' end formation in the silkworm Bombyx mori has been shown to be mediated by the 3'-to-5' exonuclease Trimmer (Trim; known as PNLDC1 in mammals), and piRNA intermediates are bound with PIWI anchored onto mitochondrial Tudor domain protein Papi. However, it remains unclear whether the Zucchini (Zuc) endonuclease and Nibbler (Nbr) 3'-to-5' exonuclease, both of which have pivotal roles in piRNA biogenesis in Drosophila, are required for piRNA processing in other species...

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PIWI-interacting RNAs (piRNAs) are germ cell-specific small RNAs essential for retrotransposon gene silencing and male germ cell development. In piRNA biogenesis, the endonuclease MitoPLD/Zucchini cleaves long, single-stranded RNAs to generate 5' termini of precursor piRNAs (pre-piRNAs) that are consecutively loaded into PIWI-family proteins. Subsequently, these pre-piRNAs are trimmed at their 3'-end by an exonuclease called Trimmer. Recently, poly(A)-specific ribonuclease-like domain-containing 1 (PNLDC1) was identified as the pre-piRNA Trimmer in silkworms...

Piwi-interacting RNAs are small regulatory RNAs with key roles in transposon silencing and regulation of gametogenesis. The production of mature piwi-interacting RNAs requires a critical step of trimming piwi-interacting RNA intermediates to achieve optimally sized piwi-interacting RNAs. The poly(A)-specific ribonuclease family deadenylase PNLDC1 is implicated in piwi-interacting RNA trimming in silkworms. The physiological function of PNLDC1 in mammals remains unknown. Using Pnldc1-deficient mice, here we show that PNLDC1 is required for piwi-interacting RNA biogenesis, transposon silencing, and spermatogenesis...

No abstract text is available yet for this article.

Deadenylases belong to an expanding family of exoribonucleases involved mainly in mRNA stability and turnover, with the exception of PARN which has additional roles in the biogenesis of several important non-coding RNAs, including miRNAs and piRNAs. Recently, PARN in C. elegans and its homolog PNLDC1 in B. mori were reported as the elusive trimmers mediating piRNA biogenesis. In addition, characterization of mammalian PNLDC1 in comparison to PARN, showed that is specifically expressed in embryonic stem and germ cells, as well as during early embryo development...

PNLDC1 is a homologue of poly(A) specific ribonuclease (PARN), a known deadenylase with additional role in processing of non-coding RNAs. Both enzymes were reported recently to participate in piRNA biogenesis in silkworm and C. elegans, respectively. To get insights on the role of mammalian PNLDC1, we characterized the human and mouse enzymes. PNLDC1 shows limited conservation compared to PARN and represents an evolutionary related but distinct group of enzymes. It is expressed specifically in mouse embryonic stem cells, human and mouse testes and during early mouse embryo development, while it fades during differentiation...

Affective psychoses are a group of severe psychiatric disorders, including schizoaffective disorder and bipolar I disorder, together affecting ∼1% of the population. Despite their high heritability, the molecular genetics and neurobiology of affective psychosis remain largely elusive. Here, we describe the identification of a structural genetic variant segregating with affective psychosis in a family with multiple members suffering from bipolar I disorder or schizoaffective disorder, bipolar type. A balanced translocation involving chromosomes 6 and 15 was detected by karyotyping and fluorescence in-situ hybridization (FISH)...