MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

MicroRNAs: Target Recognition and Regulatory Functions

Some pathogens and pests deliver small RNAs (sRNAs) into host cells to suppress host immunity. Conversely, hosts also transfer sRNAs into pathogens and pests to inhibit their virulence. Although sRNA trafficking has been observed in a wide variety of interactions, how sRNAs are transferred, especially from hosts to pathogens and pests, is still unknown. Here, we show that host Arabidopsis cells secrete exosome-like extracellular vesicles to deliver sRNAs into fungal pathogen Botrytis cinerea . These sRNA-containing vesicles accumulate at the infection sites and are taken up by the fungal cells. Transferred host sRNAs induce silencing of fungal genes critical for pathogenicity. Thus, Arabidopsis has adapted exosome-mediated cross-kingdom RNA interference as part of its immune responses during the evolutionary arms race with the pathogen.

http://science.sciencemag.org/content/sci/early/2018/05/16/science.aar4142.full.pdf

Plants send small RNAs in extracellular vesicles to fungal pathogen to silence virulence genes.

Some long noncoding RNAs (lncRNAs) play important roles in the regulation of gene expression by acting as competing endogenous RNAs (ceRNAs). However, the roles of lncRNA associated-ceRNAs in oncogenesis are not fully understood. Here, based on lncRNA microarray data of gastric cancer, bioinformatic algorithm miRcode and microRNA (miRNA) targets database TarBase, we first constructed an lncRNA-miRNA-mRNA network. Then, we confirmed it by data of six types of other cancer including head and neck squamous cell carcinoma, prostate cancer, papillary thyroid carcinoma, pituitary gonadotrope tumors, ovarian cancer, and chronic lymphocytic leukemia. The results showed a clear cancer-associated ceRNA network. Eight lncRNAs (AC009499.1, GACAT1, GACAT3, H19, LINC00152, AP000288.2, FER1L4, and RP4-620F22.3) and nine miRNAs (miR-18a-5p, miR-18b-5p, miR-19a-3p, miR-20b-5p, miR-106a-5p, miR-106b-5p, miR-31-5p, miR-139-5p, and miR-195-5p) were involved. For instance, through its miRNA response elements (MREs) to compete for miR-106a-5p, lncRNA-FER1L4 regulates the expression of PTEN, RB1, RUNX1, VEGFA, CDKN1A, E2F1, HIPK3, IL-10, and PAK7. Furthermore, cellular experimental results indicated that FER1L4-small interfering RNA (siRNA) simultaneously suppressed FER1L4 and RB1 mRNA level. These results suggest that lncRNAs harbor MREs and play important roles in post-transcriptional regulation in cancer.

/pdf/long-noncoding-rna-associated-competing-endogenous-rnas-in-1yh3ju9naa.pdf

Long noncoding RNA associated-competing endogenous RNAs in gastric cancer

Contents 1002 I. 1002 II. 1007 III. 1010 IV. 1013 1013 References 1013 SUMMARY: MicroRNAs (miRNAs) are small non-coding RNAs, of typically 20-24 nt, that regulate gene expression post-transcriptionally through sequence complementarity. Since the identification of the first miRNA, lin-4, in the nematode Caenorhabditis elegans in 1993, thousands of miRNAs have been discovered in animals and plants, and their regulatory roles in numerous biological processes have been uncovered. In plants, research efforts have established the major molecular framework of miRNA biogenesis and modes of action, and are beginning to elucidate the mechanisms of miRNA degradation. Studies have implicated restricted and surprising subcellular locations in which miRNA biogenesis or activity takes place. In this article, we summarize the current knowledge on how plant miRNAs are made and degraded, and how they repress target gene expression. We discuss not only the players involved in these processes, but also the subcellular sites in which these processes are known or implicated to take place. We hope to raise awareness that the cell biology of miRNAs holds the key to a full understanding of these enigmatic molecules.

/pdf/the-how-and-where-of-plant-micrornas-2bjqoyo3gv.pdf

The 'how' and 'where' of plant microRNAs.

Natural products for the treatment of type 2 diabetes mellitus: Pharmacology and mechanisms.

Construction of short tandem target mimic (STTM) to block the functions of plant and animal microRNAs

MicroRNAs as pharmacological targets in diabetes

Differentially Expressed MicroRNA-483 Confers Distinct Functions in Pancreatic β- and α-Cells.

Blueberry is rich in bioactive substances and possesses powerful antioxidant potential, which can protect against oxidant-induced and inflammatory cell damage and cytotoxicity. The aim of this study was to determine how blueberry affects glucose metabolism and pancreatic β-cell proliferation in high fat diet (HFD)-induced obese mice. Wild type male mice at age of 4 weeks received two different kinds of diets: high-fat diet (HFD) containing 60% fat or modified HFD supplemented with 4% (wt:wt) freeze-dried whole blueberry powder (HFD + B) for 14 weeks. A separate experiment was performed in mice fed with low-fat diet (LFD) containing 10% fat or modified LFD + B supplemented with 4% (wt:wt) freeze-dried whole blueberry powder. The metabolic parameters including blood glucose and insulin levels, glucose and insulin tolerances were measured. Blueberry-supplemented diet significantly increased insulin sensitivity and glucose tolerance in HFD + B mice compared to HFD mice. However, no difference was observed in blood glucose and insulin sensitivity between LFD + B and LFD mice. In addition, blueberry increased β-cell survival and prevented HFD-induced β-cell expansion. The most important finding was the observation of presence of small scattered islets in blueberry treated obese mice, which may reflect a potential role of blueberry in regenerating pancreatic β-cells. Blueberry-supplemented diet can prevent obesity-induced insulin resistance by improving insulin sensitivity and protecting pancreatic β-cells. Blueberry supplementation has the potential to protect and improve health conditions for both type 1 and type 2 diabetes patients.

/pdf/whole-blueberry-protects-pancreatic-beta-cells-in-diet-1vj234psmj.pdf

Whole blueberry protects pancreatic beta-cells in diet-induced obese mouse.

Pancreatic β-cell dysfunction is central to the development and progression of type 2 diabetes. Dysregulation of microRNAs (miRNAs) has been associated with pancreatic islet dysfunction in type 2 diabetes. Previous study has shown that miR-483 is expressed relatively higher in β-cells than in α-cells. To explore the physiological function of miR-483, we generated a β-cell-specific knockout mouse model of miR-483. Loss of miR-483 enhances high-fat diet-induced hyperglycemia and glucose intolerance by the attenuation of diet-induced insulin release. Intriguingly, mice with miR-483 deletion exhibited loss of β-cell features, as indicated by elevated expression of aldehyde dehydrogenase family 1, subfamily A3 (Aldh1a3), a marker of β-cell dedifferentiation. Moreover, Aldh1a3 was validated as a direct target of miR-483 and overexpression of miR-483 repressed Aldh1a3 expression. Genetic ablation of miR-483 also induced alterations in blood lipid profile. Collectively, these data suggest that miR-483 is critical in protecting β-cell function by repressing the β-cell disallowed gene Aldh1a3. The dysregulated miR-483 may impair insulin secretion and initiate β-cell dedifferentiation during the development of type 2 diabetes.

/pdf/microrna-483-protects-pancreatic-b-cells-by-targeting-3k8c02fpwo.pdf

Yiping Mao

Papers

Construction of short tandem target mimic (STTM) to block the functions of plant and animal microRNAs

MicroRNAs as pharmacological targets in diabetes

Differentially Expressed MicroRNA-483 Confers Distinct Functions in Pancreatic β- and α-Cells.

Whole blueberry protects pancreatic beta-cells in diet-induced obese mouse.

microRNA-483 Protects Pancreatic β-Cells by Targeting ALDH1A3.