Role of miRNAs and siRNAs in biotic and abiotic stress responses of plants

Small, non-coding RNAs are a distinct class of regulatory RNAs in plants and animals that control a variety of biological processes. In plants, several classes of small RNAs with specific sizes and dedicated functions have evolved through a series of pathways. The major classes of small RNAs include microRNAs (miRNAs) and small interfering RNAs (siRNAs), which differ in their biogenesis. miRNAs control the expression of cognate target genes by binding to reverse complementary sequences, resulting in cleavage or translational inhibition of the target RNAs. siRNAs have a similar structure, function, and biogenesis as miRNAs but are derived from long double-stranded RNAs and can often direct DNA methylation at target sequences. Besides their roles in growth and development and maintenance of genome integrity, small RNAs are also important components in plant stress responses. One way in which plants respond to environmental stress is by modifying their gene expression through the activity of small RNAs. Thus, understanding how small RNAs regulate gene expression will enable researchers to explore the role of small RNAs in biotic and abiotic stress responses. This review focuses on the regulatory roles of plant small RNAs in the adaptive response to stresses. This article is part of a Special Issue entitled: Plant gene regulation in response to abiotic stress.     

DNA methylation in plants: relationship to small RNAs and histone modifications, and functions in transposon inactivation

DNA methylation is a type of epigenetic marking that strongly influences chromatin structure and gene expression in plants and mammals. Over the past decade, DNA methylation has been intensively investigated in order to elucidate its control mechanisms. These studies have shown that small RNAs are involved in the induction of DNA methylation, that there is a relationship between DNA methylation and histone methylation, and that the base excision repair pathway has an important role in DNA demethylation. Some aspects of DNA methylation have also been shown to be shared with mammals, suggesting that the regulatory pathways are, in part at least, evolutionarily conserved. Considerable progress has been made in elucidating the mechanisms that control DNA methylation; however, many aspects of the mechanisms that read the information encoded by DNA methylation and mediate this into downstream regulation remain uncertain, although some candidate proteins have been identified. DNA methylation has a vital role in the inactivation of transposons, suggesting that DNA methylation is a key factor in the evolution and adaptation of plants.     

胃癌相关miRNA表达的表观遗传学调控机制

胃癌是人类最常见的肿瘤之一,其发病机制尚不完全清楚.微小RNA(microRNA,miRNA)是一组最近发现的长度为22个核苷酸左右的非编码RNA,具有负性调控基因表达的功能.本文对miRNA在胃癌发生中的作用及其表达调控机制进行综述.不断有文献显示,miRNA在多种肿瘤(包括胃癌)的发生过程中发挥着重要作用.作者和其他研究人员发现,miRNA的表达异常(如:miR-421和miR-21的上调或/和miR-31和miR-218的下调等)与胃癌的发生相关,提示miRNA是胃癌发生的重要因素.目前,miRNA表达的分子机制尚未完全明了.最近研究较清楚地显示,miRNA的表达受到DNA甲基化和组蛋白修饰等机制的调控.这说明,胃癌相关miRNA的表达水平受到表观遗传机制的调控。     

Epigenetic regulation of insulin-like growth factor binding protein-3 (IGFBP-3) in cancer

Epigenetics refers to heritable changes in gene expression that are independent of alterations in DNA sequence. It is now accepted that disruption of epigenetic mechanisms plays a key role in the pathogenesis of cancer: culminating in altered gene function and malignant cellular transformation. DNA methylation and histone modifications are the most widely studied changes but non-coding RNAs such as miRNAs are also considered part of the epigenetic machinery. The insulin-like growth factor (IGF) axis is composed of two ligands, IGF-I and –II, their receptors and six high affinity IGF binding proteins (IGFBPs). The IGF axis plays a key role in cancer development and progression. As IGFBP genes have consistently been identified among the most common to be aberrantly altered in tumours, this review will focus on epigenetic regulation of IGFBP-3 in cancer for which the majority of evidence has been obtained.     

New advances of microRNAs in the pathogenesis of rheumatoid arthritis,with a focus on the crosstalk between DNA methylation and the microRNA machinery

Rheumatoid arthritis (RA) is a symmetrical polyarticular disease of unknown aetiology that affects primarily the articular cartilage and bone. Characteristic features of RA pathogenesis are persistent inflammation, synovium hyperplasia and cartilage erosion accompanied by joint swelling and joint destruction. Several lines of evidence have showed a crucial role of activated fibroblast-like synoviocytes (FLS) in the pathogenesis of RA. MicroRNAs (miRNAs) are endogenous, single-stranded, non-coding RNAs with about 21 nucleotides in length and have been detected in a variety of sources, including tissues, serum, and other body fluids, such as saliva. In light of key roles of miRNAs in the regulation of gene expression, miRNAs influence a wide range of physiological and pathological processes. For example, miRNAs are evident in various malignant and nonmalignant diseases, and accumulating evidence also shows that miRNAs have important roles in the pathogenesis of RA. It has been demonstrated that miRNAs can be aberrantly expressed even in the different stages of RA progression, allowing miRNAs to help understand the pathogenesis of the disease, to act as important biomarkers, and to monitor the disease severity and the effects of drug treatment. In addition, miRNAs are emerging as potential targets for new therapeutic strategies of this kind of autoimmune disorders. The ultimate goal is the identification of miRNA targets that could be manipulated through specific therapies, aiming at activation or inhibition of specific miRNAs responsible for the RA development. In this review, the importance of miRNAs in the pathogenesis of RA is discussed systematically, with particular emphasis on the role of the crosstalk between DNA methylation and the microRNA machinery.     

Novel transcriptome data analysis implicates circulating microRNAs in epigenetic inheritance in mammals

Experimental evidence supports a role of mobile small non-coding RNAs in mediating soma to germline hereditary information transfer in epigenetic inheritance in plants and worms. Similar evidence in mammals has not been reported so far. In this bioinformatic analysis, differentially expressed microRNAs (miRNAs) or mRNAs reported previously in genome level expression profiling studies related to or relevant in epigenetic inheritance in mammals were examined for circulating miRNA association. The reported sets of differentially expressed miRNAs or miRNAs that are known to target the reported sets of differentially expressed genes, in that order, showed enrichment of circulating miRNAs across environmental factors, tissues, life cycle stages, generations, genders and species. Circulating miRNAs commonly representing the expression profiles enriched various epigenetic processes. These results provide bioinformatic evidence for a role of circulating miRNAs in epigenetic inheritance in mammals.     

Sweating the small stuff: microRNA discovery in plants

The class of small RNAs known as microRNAs (miRNAs) has a demonstrated role in the negative regulation of gene expression in both plants and animals. These small molecules have been shown to play a critical role in a wide range of developmental and physiological pathways. Although hundreds of different miRNAs have now been identified using cloning and computational approaches, characterization of their targets and biological roles has been more limited. New sequencing technologies promise to accelerate the sequencing of small RNAs and additional genetic and genomic strategies are being applied to assess their regulatory function on RNA targets. These technologies will enable the identification of large numbers of small RNAs from diverse species, and comparative genomics approaches based on these data are likely to identify additional miRNAs. Combined with bioinformatics and experimental approaches to separate miRNAs from short-interfering RNAs (siRNAs), the pace of miRNA discovery is likely to accelerate, leading to an improved understanding of miRNA function and biological significance.     

Recapitulation of short RNA-directed translational gene silencing in vitro

microRNAs (miRNAs) are a large class of endogenous short RNAs that repress gene expression. Many miRNAs are conserved throughout evolution, and dysregulation of miRNA pathways has been correlated with an increasing number of human diseases. In animals, miRNAs typically bind to the 3' untranslated region (3'UTR) of target mRNAs with imperfect sequence complementarity and repress translation. Despite their importance in regulating biological processes in numerous organisms, the mechanisms of miRNA function are largely unknown. Here, we report in vitro reactions for miRNA-directed translational gene silencing. These reactions faithfully recapitulate known in vivo hallmarks of mammalian miRNA function, including a requirement for a 5' phosphate and perfect complementarity to the mRNA target in the 5' seed region. Translational gene silencing by miRNAs in vitro requires target mRNAs to possess a 7-methyl G cap and a polyA tail, whereas increasing polyA tail length alone can increase miRNA silencing activity.     

Small RNAs in regulating temperature stress response in plants

Due to global climate change, temperature stress has become one of the primary causes of crop losses worldwide. Much progress has been made in unraveling the complex stress response mechanisms in plants, particularly in the identification of temperature stress responsive protein‐coding genes. Recently discovered microRNAs (miRNAs) and endogenous small‐interfering RNAs (siRN As) have also been demonstrated as important players in plant temperature stress response. Using high‐throughput sequencing, many small RNAs, especially miRNAs, have been identified to be triggered by cold or heat. Subsequently, several studies have shown an important functional role for these small RNAs in cold or heat tolerance. These findings greatly broaden our understanding of endogenous small RNAs in plant stress response control. Here, we highlight new findings regarding the roles of miRNAs and siRNAs in plant temperature stress response and acclimation. We also review the current understanding of the regulatory mechanisms of small RNAs in temperature stress response, and explore the outlook for the use of these small RNAs in molecular breeding for improvement of temperature stress tolerance in plants.