Paternal environmental exposure-induced spermatozoal small noncoding RNA alteration meditates the intergenerational epigenetic inheritance of multiple diseases

Studies of human and mammalian have revealed that environmental exposure can affect paternal health conditions as well as those of the offspring.However,studies that explore the mechanisms that meditate this transmission are rare.Recently,small noncoding RNAs(sncRNAs)in sperm have seemed crucial to this transmission due to their alteration in sperm in response to environmental exposure,and the methodology of microinjection of isolated total RNA or sncRNAs or synthetically identified sncRNAs gradually lifted the veil of sncRNA regulation during intergenerational inheritance along the male line.Hence,by reviewing relevant literature,this study intends to answer the following research concepts:(1)paternal environmental factors that can be passed on to offspring and are attributed to spermatozoal sncRNAs,(2)potential role of paternal spermatozoal sncRNAs during the intergenerational inheritance process,and(3)the potential mechanism by which spermatozoal sncRNAs meditate intergenerational inheritance.In summary,increased attention highlights the hidden wonder of spermatozoal sncRNAs during intergenerational inheritance.Therefore,in the future,more studies should focus on the origin of RNA alteration,the target of RNA regulation,and how sncRNA regulation during embryonic development can be sustained even in adult offspring.

Small noncoding RNAs play superior roles in maintaining hematopoietic stem cell homeostasis

The maintenance of the mammalian blood system depends on hematopoietic stem cells(HSCs),which are a rare class of adult stem cells with self-renewal and multilineage differentiation capacities.The homeostasis of hematopoietic stem cells is finely tuned by a variety of endogenous and exogenous regulatory factors,and disrupted balance will lead to hematological diseases including leukemia and anemia.Recently,emerging studies have illustrated the cellular and molecular mechanisms underlying the regulation of HSC homeostasis.Particularly,the rapid development of second-generation sequencing technologies has uncovered that many small noncoding RNAs(ncRNAs)are highly expressed in HSCs,including snoRNAs,miRNAs,tsRNAs,circular RNAs,etc.In this study,we will summarize the essential roles and regulatory mechanisms of these small ncRNAs in maintaining HSC homeostasis.Overall,this review provides up-to-date information in the regulation of HSC homeostasis by small ncRNAs,which sheds light into the development of therapeutic strategies against hematopoietic malignancies.

Mechanism of lncRNA SNHG19 miR-299-5p MAPK6 signaling axis promoting metastasis of non-small cell lung cancer cells

Objective The aim of this study was to explore the mechanism behind lncRNA small nucleolar RNA host gene 19(lncRNA SNHG19)/microrNA-299-5P(miR-299-5p)/mitogen-activated protein kinase 6(MAPK6)signaling axis promoting metastasis of non-small cell lung cancer(NSCLC).Methods To analyze the abnormal expression of lncRNAs in NSCLC,50 surgically resected NSCLC and adjacent tissue samples were collected from August 2021 to August 2022.The mRNA expression levels of lncRNA SNHG19,Mir-299-5p,and MAPK6 were detected by qRT-PCR.The functions of lncRNA SNHG19,Mir-299-5p and MAPK6 were investigated by CCK-8,clone formation,EdU,scratch,Transwell western blotting(WB)and in vivo xenograft assay.RNA fluorescence in-situ hybridization(FISH),RNA pull-down,dual luciferase reporter,and RNA co-immunoprecipitation assays were used to explore the mechanism of action between lncRNA SNHG19,miR-299-5p,and MAPK6.Results High expression of lncRNA SNHG19 was correlated with poor prognosis,tumor size,lymph node metastasis,and TNM stage in NSCLC patients(P<0.05).Cell function experiments showed that lncRNA SNHG19 could improve the proliferation,clone formation,migration,and invasion ability of A549 cells both in vitro and in vivo(all P<0.05)and increased the relative expression levels of vimentin and MAPK6(P<0.05).The relative expression level of E-cadherin was decreased(P<0.05).lncRNA SNHG19 can interact with Mir-299-5p and regulate the expression level of MAPK6.Conclusion lncRNA SNHG19 is upregulated in NSCLC tissues and cells,and its high expression is associated with tumor progression and poor survival.Moreover,it can act as a molecular sponge for Mir-299-5p to regulate MAPK6 expression and promote the proliferation and metastasis of A549 cells.

Design of artificial small regulatory trans-RNA for gene knockdown in Bacillus subtilis

Bacillus subtilis as the Gram-positive model bacterium has been widely used in synthetic biology and biotechnology while the regulatory RNA tools for B.subtilis are still not fully explored.Here,a bottom-up approach is proposed for designing artificial trans-acting sRNAs.By engineering the intrinsic sRNA SR6,a minimized core scaffold structure consisting of an 8 bp stem,a 4 nt loop,and a 9 nt polyU tail was generated and proven to be sufficient for constructing sRNAs with strong repression activity(83%).Moreover,we demonstrate this artificial sRNA system functions well in an hfq-independent manner and also achieves strong repression efficiency in Escherichia coli(above 80%).A structure-based sRNA design principle was further developed for the automatic generation of custom sRNAs with this core scaffold but various sequences,which facilitates the manipulation and avoids structure disruption when fusing any base-pairing sequence.By applying these auto-designed sRNAs,we rapidly modified the cell morphology and biofilm formation,and regulated metabolic flux toward acetoin biosynthesis.This sRNA system with cross-species regulatory activities not only enriched the gene regulation toolkit in synthetic biology for B.subtilis and E.coli but also enhanced our understanding of trans-acting sRNAs.

Knockout of glutathione peroxidase 5 down-regulates the piRNAs in the caput epididymidis of aged mice

The mammalian epididymis not only plays a fun dame ntal role in the maturati on of spermatozoa,but also provides protecti on agai nst various stressors.The foremost among these is the threat posed by oxidative stress,which arises from an imbalance in reactive oxygen species and can elicit damage to cellular lipids,proteins,and nucleic acids.In mice,the risk of oxidative damage to spermatozoa is mitigated through the expression and secretion of glutathione peroxidase 5(GPX5)as a major luminal scavenger in the proximal caput epididymidal segment.Accordingly,the loss of GPX5^-/-mediated protection leads to impaired DNA integrity in the spermatozoa of aged Gpx57 mice.To explore the underlying mechanism,we have conducted transcriptomic analysis of caput epididymidal epithelial cells from aged(13 months old)Gpx5^-/-m mice.This analysis revealed the dysregulation of several thousand epididymal mRNA transcripts,in eluding the downregulation of a subgroup of piRNA pathway gen es,in aged Gpx5^-/-mice.In agreeme nt with these fin dings,we also observed the loss of piRNAs,which potentially bind to the P-element-induced wimpy testis(PlWI)-like proteins PIWIL1 and PIWIL2.The absence of these piRNAs was correlated with the elevated mRNA levels of their putative gene targets in the caput epididymidis of Gpx5^-/-mice.Importantly,the oxidative stress response genes tend to have more targeting piRNAs,and many of them were among the top increased genes upon the loss of GPX5^-/-.Taken together,our findings suggest the existence of a previously uncharacterized somatic piRNA pathway in the mammalian epididymis and its possible invoIvement in the aging and oxidative stress-mediated responses.