![]() ![]() MiRNA biogenesis starts with the processing of RNA polymerase II/III transcripts post- or co-transcriptionally ( 14). Finally, we have summarized the secretion and circulation of miRNAs and the potential roles of extracellular miRNAs in mediating intercellular communications. Moreover, we have discussed the dynamics of miRNA intracellular localization and function. In this review, we have provided a brief overview of the different pathways of miRNA biogenesis in animals and the expanding complexity of their regulation of gene expression. Extracellular miRNAs have been widely reported as potential biomarkers for a variety of diseases and they also serve as signaling molecules to mediate cell-cell communications ( 21– 23). ![]() ![]() In addition, miRNAs are secreted into extracellular fluids. Aberrant expression of miRNAs is associated with many human diseases ( 19, 20). MiRNAs are critical for normal animal development and are involved in a variety of biological processes ( 18). Recent studies have suggested that miRNAs are shuttled between different subcellular compartments to control the rate of translation, and even transcription ( 17). Furthermore, miRNAs have been shown to activate gene expression under certain conditions ( 16). However, interaction of miRNAs with other regions, including the 5′ UTR, coding sequence, and gene promoters, have also been reported ( 15). In most cases, miRNAs interact with the 3′ UTR of target mRNAs to suppress expression ( 14). Most miRNAs are transcribed from DNA sequences into primary miRNAs (pri-miRNAs) and processed into precursor miRNAs (pre-miRNAs) and mature miRNAs. MiRNAs are small non-coding RNAs, with an average 22 nucleotides in length. New miRNAs are still being discovered ( 13) and their roles in gene regulation are well recognized. Since then, miRNAs have been detected in all animal model systems and some were shown to be highly conserved across species ( 9– 12). Therefore, they proposed that lin-4 regulates lin-14 at the post-transcriptional level ( 2). They also found that lin-14 was post-transcriptionally downregulated through its 3′ untranslated region (UTR) and that lin-4 had a complementary sequence to that of the 3′ UTR of lin-14 ( 1). Both Ambros and Ruvkun continued to study lin-4 and lin-14 after leaving the Horvitz's lab, only to discover later that lin-4 was not a protein-coding RNA but indeed a small non-coding RNA ( 7, 8). Later in 1987, the same group found that a mutation in lin-4 had an opposite phenotype to a mutation in another gene, lin-14, yet a lin-14 suppressor mutation in a null-lin-4 line was wildtype ( 5, 6). Years before, lin-4 was characterized by the Horvitz's lab as one of the genes that regulate temporal development of C. The discovery of the first microRNA (miRNA), lin-4, in 1993 by the Ambros and Ruvkun groups in Caenorhabditis elegans ( 1, 2) has revolutionized the field of molecular biology. We also summarize the current knowledge of the dynamics of miRNA action and of the secretion, transfer, and uptake of extracellular miRNAs. ![]() In this review, we provide an update on canonical and non-canonical miRNA biogenesis pathways and various mechanisms underlying miRNA-mediated gene regulations. Extracellular miRNAs function as chemical messengers to mediate cell-cell communication. miRNAs can be secreted into extracellular fluids and transported to target cells via vesicles, such as exosomes, or by binding to proteins, including Argonautes. The interaction of miRNAs with their target genes is dynamic and dependent on many factors, such as subcellular location of miRNAs, the abundancy of miRNAs and target mRNAs, and the affinity of miRNA-mRNA interactions. Under certain conditions, miRNAs can also activate translation or regulate transcription. However, interaction of miRNAs with other regions, including the 5′ UTR, coding sequence, and gene promoters, have also been reported. In most cases, miRNAs interact with the 3′ untranslated region (3′ UTR) of target mRNAs to induce mRNA degradation and translational repression. The majority of miRNAs are transcribed from DNA sequences into primary miRNAs and processed into precursor miRNAs, and finally mature miRNAs. MicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in regulating gene expression. Department of Biology, York University, Toronto, ON, Canada.Jacob O'Brien Heyam Hayder Yara Zayed Chun Peng * ![]()
0 Comments
Leave a Reply. |
Details
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |