We have yet to develop a fundamental understanding of the molecular complexities of human spermatozoa. This encompasses the unique packaging and structure of the sperm genome along with their paternally derived RNAs in preparation for their delivery to the egg. The diversity of these transcripts is vast, including several anti-sense molecules resembling known regulatory micro-RNAs. The field is still grasping with its delivery to the oocyte at fertilization and possible significance. It remains tempting to analogize them to maternally-derived transcripts active in early embryo patterning. Irrespective of their role in the embryo, their use as a means to assess male factor infertility is promising.
DNA ; genetics ; metabolism ; Humans ; Male ; RNA, Messenger ; genetics ; Spermatozoa ; metabolism

Animals ; Biological Evolution ; Fungi ; genetics ; Plants ; genetics ; RNA, Messenger ; metabolism

Alternative splicing (AS) is an evolutionarily conserved mechanism that removes introns and ligates exons to generate mature messenger RNAs (mRNAs), extremely improving the richness of transcriptome and proteome. Both mammal hosts and pathogens require AS to maintain their life activities, and inherent physiological heterogeneity between mammals and pathogens makes them adopt different ways to perform AS. Mammals and fungi conduct a two-step transesterification reaction by spliceosomes to splice each individual mRNA (named cis -splicing). Parasites also use spliceosomes to splice, but this splicing can occur among different mRNAs (named trans -splicing). Bacteria and viruses directly hijack the host's splicing machinery to accomplish this process. Infection-related changes are reflected in the spliceosome behaviors and the characteristics of various splicing regulators (abundance, modification, distribution, movement speed, and conformation), which further radiate to alterations in the global splicing profiles. Genes with splicing changes are enriched in immune-, growth-, or metabolism-related pathways, highlighting approaches through which hosts crosstalk with pathogens. Based on these infection-specific regulators or AS events, several targeted agents have been developed to fight against pathogens. Here, we summarized recent findings in the field of infection-related splicing, including splicing mechanisms of pathogens and hosts, splicing regulation and aberrant AS events, as well as emerging targeted drugs. We aimed to systemically decode host-pathogen interactions from a perspective of splicing. We further discussed the current strategies of drug development, detection methods, analysis algorithms, and database construction, facilitating the annotation of infection-related splicing and the integration of AS with disease phenotype.
Animals ; Alternative Splicing/genetics* ; RNA Splicing ; Spliceosomes/metabolism* ; RNA, Messenger/metabolism* ; Communicable Diseases/genetics* ; Mammals/metabolism*

Parasite-derived non-coding RNAs (ncRNAs) not only contribute to life activities of parasites, and microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA) may generate a competitive endogenous RNA (ceRNA) regulatory network with host miRNAs and mRNAs via extracellular vesicles, thereby participating in infection and pathogenic processes. This article presents an overview of characterizing ncRNAs derived from parasites and the cross-species regulatory role of parasite-derived ncRNAs in host gene expression and its underlying mechanisms.
Animals ; Parasites ; Gene Regulatory Networks ; MicroRNAs/metabolism* ; RNA, Messenger/genetics* ; RNA, Circular/genetics* ; RNA, Competitive Endogenous

Emerging evidence suggests that intron-detaining transcripts (IDTs) are a nucleus-detained and polyadenylated mRNA pool for cell to quickly and effectively respond to environmental stimuli and stress. However, the underlying mechanisms of detained intron (DI) splicing are still largely unknown. Here, we suggest that post-transcriptional DI splicing is paused at the Bact state, an active spliceosome but not catalytically primed, which depends on Smad Nuclear Interacting Protein 1 (SNIP1) and RNPS1 (a serine-rich RNA binding protein) interaction. RNPS1 and Bact components preferentially dock at DIs and the RNPS1 docking is sufficient to trigger spliceosome pausing. Haploinsufficiency of Snip1 attenuates neurodegeneration and globally rescues IDT accumulation caused by a previously reported mutant U2 snRNA, a basal spliceosomal component. Snip1 conditional knockout in the cerebellum decreases DI splicing efficiency and causes neurodegeneration. Therefore, we suggest that SNIP1 and RNPS1 form a molecular brake to promote spliceosome pausing, and that its misregulation contributes to neurodegeneration.
Spliceosomes/metabolism* ; Introns/genetics* ; RNA Splicing ; RNA, Messenger/genetics* ; Cell Nucleus/metabolism*

microRNA (miRNA) are small non-coding RNA molecules of 19 - 25 nucleotides in a variety of eukaryotic systems, that control gene expression at the post-transcriptional level by degrading or translational repressing target messenger RNA (mRNA). Many studies have addressed the role of miRNA in normal hematopoiesis, giving an interpretative key to the aberrant expression observed in human hematological diseases. Here, the advances of main studies on the role of miRNA in normal hematopoiesis, and identify the association of miRNA with the development, progression of myeloproliferative diseases, including miRNA and lymphopoiesis, miRNA and erythropoiesis, miRNA and megakaryopoiesis, miRNA and myelopoiesis, miRNA and myeloproliferative neoplasm with positive BCR-ABL-chronic myeloid leukemia, miRNA and myeloproliferative neoplasm with negative PCR-ABL (PV.IME, ET), and so on are reviewed.
Gene Expression Regulation ; Hematopoiesis ; genetics ; Humans ; MicroRNAs ; genetics ; metabolism ; Myeloproliferative Disorders ; genetics ; metabolism ; RNA, Messenger ; genetics

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*

To detect the expression of telomerase subunits (human telomerase reverse transcriptase, human telomerase associated protein 1 and human telomerase RNA) in gastric cancer and to examine the role that different telomerase subunits play in the gastric carcinogenesis, reverse transcription-polymerase chain reaction (RT-PCR) was used to detect telomerase subunits messenger RNA in 24 samples of gastric cancer and corresponding non-cancerous tissue. The results showed that the positive rate of hTERT mRNA from gastric cancer and corresponding non-cancerous tissues was 100% and 25%, respectively. The former was significantly higher than the latter (chi2 = 26.4, P < 0.01). The positive rate of hTEP1 mRNA from gastric cancer and corresponding non-cancerous tissues was 100% and 91.7%, respectively and no significant difference was found between them (chi2 = 2.1, P > 0.05). The positive rates of hTR for gastric cancer and corresponding non-cancerous tissues were both 100% and no significant difference existed between them. It is concluded that in contrast to hTEP1 and hTR, the up-regulation of hTERT mRNA expression may play a more important role in the development of gastric cancer.
Carrier Proteins/biosynthesis ; Carrier Proteins/genetics ; RNA/biosynthesis ; RNA/genetics ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Stomach Neoplasms/*metabolism ; Telomerase/*biosynthesis ; Telomerase/genetics

This study was aimed to explore the expression of erythropoietin receptor (EPOR) on acute leukemia cells and its clinical significance. Bone marrow of 40 patients with acute leukemia (AL) and 24 patients with normal bone marrow as control group were collected. Samples came from outpatients and inpatients in our hospital. EPOR mRNA was detected by reverse transcription-PCR. The results showed that there was EPOR expression on AL cells, the expression rate was 57.5%, and the average expression level (Gray value) was 0.3549 ± 0.2800, but both were lower than that in control group (p < 0.05). There was no significant statistic difference of expression rate between acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) (p > 0.05), and expression level of AML EPOR was higher than that of ALL (p < 0.05). It is concluded that there is EPOR expression on AL cells, while the expression rate and expression level are lower than those in control group (p < 0.05). There is no significant statistic difference of the expression rate between AML and ALL (p > 0.05), and the expression level of AML EPOR is higher than that of ALL (p < 0.05).
Case-Control Studies ; Humans ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; RNA, Messenger ; genetics ; Receptors, Erythropoietin ; genetics ; metabolism

This study aimed to explore the effect of miR-23b-3p on the differentiation of goat intramuscular preadipocytes, and to confirm whether miR-23b-3p plays its roles via targeting the PDE4B gene. Based on the pre-transcriptome sequencing data obtained previously, the miR-23b-3p, which was differentially expressed in goat intramuscular adipocytes before and after differentiation, was used as an entry point. real-time quantitative-polymerase chain reaction (qPCR) was used to detect the expression pattern of miR-23b-3p during the differentiation of goat intramuscular preadipocytes. The effects of miR-23b-3p on adipose differentiation and adipose differentiation marker genes were determined at the morphological and molecular levels. The downstream target genes of miR-23b-3p were determined using bioinformatics prediction as well as dual luciferase reporter assay to clarify the targeting relationship between miR-23b-3p and the predicted target genes. The results indicated that overexpression of miR-23b-3p reduced lipid droplet accumulation in goat intramuscular adipocytes, significantly down-regulated the expression levels of adipogenic marker genes AP2, C/EBPα, FASN, and LPL (P < 0.01). In addition, the expressions of C/EBPβ, DGAT2, GLUT4 and PPARγ were significantly downregulated (P < 0.05). After interfering with the expression of miR-23b-3p, lipid droplet accumulation was increased in goat intramuscular adipocytes. The expression levels of ACC, ATGL, AP2, DGAT2, GLUT4, FASN and SREBP1 were extremely significantly up-regulated (P < 0.01), and the expression levels of C/EBPβ, LPL and PPARγ were significantly up-regulated (P < 0.05). It was predicted that PDE4B might be a target gene of miR-23b-3p. The mRNA expression level of PDE4B was significantly decreased after overexpression of miR-23b-3p (P < 0.01), and the interference with miR-23b-3p significantly increased the mRNA level of PDE4B (P < 0.05). The dual luciferase reporter assay indicated that miR-23b-3p had a targeting relationship with PDE4B gene. MiR-23b-3p regulates the differentiation of goat intramuscular preadipocytes by targeting the PDE4B gene.
Animals ; MicroRNAs/metabolism* ; Goats/genetics* ; PPAR gamma/metabolism* ; Adipogenesis/genetics* ; Cell Differentiation/genetics* ; Luciferases ; RNA, Messenger