Review From the lab to the hospital: new ideas in miRNA medicine
AbstractSince a single miRNA may control many target genes across several pathways in a cell, it is clear that miRNAs are very potent genetic regulators. Because of this characteristic, miRNAs are promising therapeutic agents for reversing the altered cellular processes that characterize disease phenotypes. MiRNAs' strength is in their ability to regulate a wide variety of cellular processes, but this also makes them vulnerable to off-target effects. In this review, we highlight the primary obstacles and provide approaches to resolving these issues in order to advance miRNA therapeutics. Methods that have advanced to clinical trials are highlighted in particular. What potential do medicinal uses of miRNA hold? The function of microRNAs (miRNAs; see Glossary) is to regulate the expression of proteins after their transcription. throughout 2300 unique miRNAs have been identified in human cells [1, 2, 3]. Their levels of expression vary throughout time and across various types of tissue. Box 1 provides key information on the biosynthesis and function of miRNAs. The following discussion focuses on miRNA fidelity criteria. MicroRNA biogenesis in cells. Sequences encoding microRNAs may be found in the intronic sections of protein-coding genes, the exonic regions, or the intergenic regions. They might be under the control of their host genes' promoters or have their own . Primary miRNAs (pri-miRNAs) are transcribed from miRNA encoding sequences by RNA polymerase II or III into mature miRNAs (miRNAs), which may be several thousand nucleotides in length and have a hairpin structure (the biogenesis of miRNAs has been extensively discussed elsewhere; see, for example, [103., 104., 105.]). The Drosha-DGCR8 microprocessor complex in the nucleus further processes pri-miRNAs to produce a miRNA precursor (pre-miRNA) of around 70 nucleotides in length. In a noncanonical biogenesis, intron-encoded pre-miRNAs (mirtrons) may be directly processed together with their coencoded transcripts by spliceosomes. Once in the cytoplasm, RNase Dicer and the double-stranded RNA binding enzyme TRBP break the pre-miRNA hairpin into a miRNA duplex of around 22 nucleotides in length. The RISC is then modified to contain single strands of miRNA, enabling the ribonucleoprotein complex to attach to specific sequences within the 3' untranslated regions of messenger RNAs. The seed region, typically located between nucleotides 2 and 7 at the 5' end of the miRNA, is where reverse complementary binding occurs. This binding prevents or halts the translation process. As miRNAs are thought to regulate as much as 60% of all protein-encoding genes post-transcriptionally , they are pivotal in cellular signaling and have far-reaching effects on almost every biological activity . New data suggests that microRNAs (miRNAs) may go into the nucleus to affect gene transcription , expanding their influence on cellular signaling networks beyond their actions at the post-transcriptional level.