As regulators of gene expression in multicellular organisms, microRNAs (miRNAs) are crucial for growth and development. While a plethora of factors involved in their biogenesis and action in Arabidopsis thaliana have been described, these processes and their fine-tuning are not fully understood in plants. Here, we used plants expressing an artificial miRNA target mimic (MIM) to screen for negat...

MicroRNAs (miRNAs) are noncoding RNAs that function as key posttranscriptional regulators of gene expression. miRNA maturation is controlled by the DROSHA microprocessor complex. However, the detailed mechanism of miRNA biogenesis remains unclear. We show that the tumor suppressor breast cancer 1 (BRCA1) accelerates the processing of miRNA primary transcripts. BRCA1 increased the expressions of...

MicroRNAs (miRNAs) are short, non-coding sequences that control gene expression via translational regulation. Through interactions with the 3'-untranslated region of messenger RNA, miRNAs trigger translational repression and play a key role in developmental timing. Furthermore, many miRNA groups have now been shown to regulate various processes in tumorigenesis, including angiogenesis and metas...

MicroRNAs (miRNAs) are a class of small non-coding RNA molecules of about 22 nucleotides in length. miRNAs are highly conserved in both plants and animals, and function as gene regulators by binding to the 3'-untranslated region of target mRNAs for cleavage and/or translational repression. miRNA biogenesis, stability, and regulation of expression are strongly sequence dependent. Sequence varian...

Although much is known about microRNA (miRNA) biogenesis and the mechanism by which miRNAs regulate their targets, little is known about the regulation of miRNA stability. Mature miRNAs are stabilized by binding to Argonaute (Ago) proteins, the core components of the RNA-induced silencing complex (RISC). Recent studies suggest that interactions between miRNAs and their highly complementary targ...

MicroRNAs (miRNAs) modulate a broad range of gene expression patterns during development and tissue homeostasis, and in the pathogenesis of disease. The exquisite spatio-temporal control of miRNA abundance is made possible, in part, by regulation of the miRNA biogenesis pathway. In this review, we discuss two emerging paradigms for post-transcriptional control of miRNA expression. One paradigm ...

Relatively little is known about the regulatory mechanisms of the Drosha/DGCR8 complex, which processes miRNAs at the initial step of biogenesis. We found that histone deacetylase 1 (HDAC1) increases the expression levels of mature miRNAs despite repressing the transcription of host genes. HDAC1 is an integral component of the Drosha/DGCR8 complex and enhances miRNA processing by increasing the...

MicroRNAs are approximately 22 nucleotide-long RNAs that silence gene expression posttranscriptionally by binding to the 3' untranslated regions of target mRNAs. Although much is known about their biogenesis and biological functions, the mechanisms allowing miRNAs to silence gene expression in animal cells are still under debate. Here, we discuss current models for miRNA-mediated gene silencing...

Overexpression of ribonucleotide reductase subunit M2 (RRM2), involved in deoxyribonucleotide synthesis, drives the chemoresistance of pancreatic cancer to nucleoside analogs (e.g., gemcitabine). While silencing RRM2 by synthetic means has shown promise in reducing chemoresistance, targeting endogenous molecules, especially microRNAs (miRNAs), to advance chemotherapeutic outcomes has been poorl...

Plant MIR genes are independent transcription units that encode long primary miRNA precursors, which usually contain introns. For two miRNA genes, MIR163 and MIR161, we show that introns are crucial for the accumulation of proper levels of mature miRNA. Removal of the intron in both cases led to a drop-off in the level of mature miRNAs. We demonstrate that the stimulating effects of the intron ...