MicroRNAs grow up in the immune system

MicroRNA (miRNA) target predictions support a view in which each miRNA regulates translation and stability of several hundred messenger RNAs (mRNAs). Studies that overexpress individual miRNAs typically uncover relative subtle inhibition of the predicted targets. Accordingly, most miRNAs expressed in a given cell type may serve the function to broadly inhibit cell-type-inappropriate gene expression and deepen a pre-existing differentiation program. However, recent functional analyses of miRNAs in the immune system reveal that many cellular decisions are controlled by single miRNAs that entail significant downregulation of one or few target proteins. Investigations of these miRNA/mRNA pairs showed that miRNA-adjusted target protein levels are crucial at specific cellular transition points. Here, we will review recent advances in the regulation of the miRNA pathway and discuss how miRNAs control immune functions.     

microRNAs和自身免疫性疾病

microRNAs（miRNAs）是一类进化上保守的微小非编码RNA,通过与靶基因mRNA3’端非翻译区相互作用致使mRNA降解或翻译抑制,在转录后水平调控基因表达,进而影响细胞周期、分化及凋亡等多种细胞生理过程。nfiRNAs在免疫系统的发育及功能行使中具有重要调控作用。研究表明,miRNAs在多种自身免疫性疾病中表达异常,提示miRNAs在自身免疫性疾病的发生发展及防治中具有重大作用。     

microRNA management of NK‐cell developmental and functional programs

NK cells are innate lymphoid cells that are critical for host defense against infection, and mediate anti‐tumor responses. MicroRNAs (miRNAs) are a large family of small noncoding RNAs that target the 3′ untranslated region (UTR) of mRNAs, thereby attenuating protein translation. The expression of miRNAs within human peripheral blood and mouse splenic NK cells has been cataloged, with the majority of the miRNA sequence pool represented in the top 60 most abundantly expressed miRNAs. Global miRNA deficiency within NK cells has confirmed their critical role in NK‐cell biology, including defects in NK‐cell development and altered functionality. Studies using gain‐ and loss‐of‐function of individual miRNAs in NK cells have demonstrated the role of specific miRNAs in regulating NK‐cell development, maturation, and activation. miRNAs also regulate fundamental NK‐cell processes including cytokine production, cytotoxicity, and proliferation. This review provides an update on the intrinsic miRNA regulation of NK cells, including miRNA expression profiles, as well as their impact on NK‐cell biology. Additional profiling is needed to better understand miRNA expression within NK‐cell developmental intermediates, subsets, tissues, and in the setting of disease. Furthermore, key open questions in the field as well as technical challenges in the study of miRNAs in NK cells are highlighted.     

miRNA与缺血性疾病中的血管新生

MicroRNAs(miRNAs)是存在于真核生物中一类长度约为20~24 nt的非编码小分子单链RNA,可调控多种基因的表达。研究发现,缺血性损伤组织中一系列的miRNAs表达发生了明显变化,且其改变可显著影响缺血组织的血管新生。     

Diagnostic and theranostic microRNAs in the pathogenesis of atherosclerosis

MicroRNAs (miRNAs) are a group of small single strand and noncoding RNAs that regulate several physiological and molecular signalling pathways. Alterations of miRNA expression profiles may be involved with pathophysiological processes underlying the development of atherosclerosis and cardiovascular diseases, including changes in the functions of the endothelial cells and vascular smooth muscle cells, such as cell proliferation, migration and inflammation, which are involved in angiogenesis, macrophage function and foam cell formation. Thus, miRNAs can be considered to have a crucial role in the progression, modulation and regulation of every stage of atherosclerosis. Such potential biomarkers will enable us to predict therapeutic response and prognosis of cardiovascular diseases and adopt effective preclinical and clinical treatment strategies. In the present review article, the current data regarding the role of miRNAs in atherosclerosis were summarized and the potential miRNAs as prognostic, diagnostic and theranostic biomarkers in preclinical and clinical studies were further discussed. The highlights of this review are expected to present opportunities for future research of clinical therapeutic approaches in vascular diseases resulting from atherosclerosis with an emphasis on miRNAs.     

FGF-4 signaling is involved in mir-206 expression in developing somites of chicken embryos.

The microRNAs (miRNAs) are recently discovered short, noncoding RNAs, that regulate gene expression in metazoans. We have cloned short RNAs from chicken embryos and identified five new chicken miRNA genes. Genome analysis identified 17 new chicken miRNA genes based on sequence homology to previously characterized mouse miRNAs. Developmental Northern blots of chick embryos showed increased accumulation of most miRNAs analyzed from 1.5 days to 5 days except, the stem cell-specific mir-302, which was expressed at high levels at early stages and then declined. In situ analysis of mature miRNAs revealed the restricted expression of mir-124 in the central nervous system and of mir-206 in developing somites, in particular the developing myotome. In addition, we investigated how miR-206 expression is controlled during somite development using bead implants. These experiments demonstrate that fibroblast growth factor (FGF) -mediated signaling negatively regulates the initiation of mir-206 gene expression. This may be mediated through the effects of FGF on somite differentiation. These data provide the first demonstration that developmental signaling pathways affect miRNA expression. Thus far, miRNAs have not been studied extensively in chicken embryos, and our results show that this system can complement other model organisms to investigate the regulation of many other miRNAs.     

Deep sequencing of tomato short RNAs identifies microRNAs targeting genes involved in fruit ripening

In plants there are several classes of 21-24-nt short RNAs that regulate gene expression. The most conserved class is the microRNAs (miRNAs), although some miRNAs are found only in specific species. We used high-throughput pyrosequencing to identify conserved and nonconserved miRNAs and other short RNAs in tomato fruit and leaf. Several conserved miRNAs showed tissue-specific expression, which, combined with target gene validation results, suggests that miRNAs may play a role in fleshy fruit development. We also identified four new nonconserved miRNAs. One of the validated targets of a novel miRNA is a member of the CTR family involved in fruit ripening. However, 62 predicted targets showing near perfect complementarity to potential new miRNAs did not validate experimentally. This suggests that target prediction of plant short RNAs could have a high false-positive rate and must therefore be validated experimentally. We also found short RNAs from a Solanaceae-specific foldback transposon, which showed a miRNA/miRNA*-like distribution, suggesting that this element may function as a miRNA gene progenitor. The other Solanaceae-specific class of short RNA was derived from an endogenous pararetrovirus sequence inserted into the tomato chromosomes. This study opens a new avenue in the field of fleshy fruit biology by raising the possibility that fruit development and ripening may be under miRNA regulation.