MicroRNA: Biogenesis, Function and Role in Cancer

MicroRNA: Biogenesis, Function and Role in Cancer

2010 | Leigh-Ann MacFarlane and Paul R. Murphy
MicroRNAs (miRNAs) are small, highly conserved non-coding RNA molecules that regulate gene expression. They are transcribed by RNA polymerases II and III, generating precursors that undergo cleavage to form mature miRNAs. The conventional biogenesis pathway involves two cleavage events, one in the nucleus and one in the cytoplasm. Alternative pathways exist, differing in the number of cleavage events and enzymes involved. The sorting of miRNA precursors to different pathways is determined by their origin, sequence, and thermodynamic stability. MiRNAs function through the RNA-induced silencing complex (RISC), which targets messenger RNA (mRNA) for silencing via mRNA cleavage or translation inhibition. Recent evidence indicates that P-bodies are essential for miRNA-mediated gene silencing, with RISC assembly and silencing occurring primarily within P-bodies. The P-body model outlines miRNA sorting and shuttling between specialized compartments that house enzymes required for slicer-dependent and -independent silencing. MiRNAs are found in most eukaryotes, including humans, and regulate at least 30% of protein-coding genes. They are involved in diverse cellular and metabolic pathways and play a crucial role in gene expression regulation. MiRNA expression profiles are altered in specific tumors, suggesting their involvement in cancer development and other diseases. MiRNA expression profiling is clinically relevant to cancer diagnosis, progression, and outcome. MiRNAs are small, single-stranded, non-coding RNA molecules that bind to target mRNA to prevent protein production through two mechanisms. Mature miRNAs are generated through two-step cleavage of primary miRNA (pri-miRNA), which incorporates into the RISC complex. The level of complementarity between the miRNA and target mRNA determines the silencing mechanism, either cleavage of target mRNA or translation inhibition. MiRNA biogenesis involves nuclear and cytoplasmic cleavage events by Drosha and Dicer. The nuclear cleavage of pri-miRNA by the microprocessor complex generates pre-miRNA, which is exported to the cytoplasm for further processing by Dicer. MiRNA biogenesis is a two-step process involving nuclear and cytoplasmic cleavage events. Intergenic miRNAs are transcribed by RNA polymerase II or III, while coding-intronic miRNAs are transcribed by RNA polymerase II as part of the pre-mRNA. MiRNA excision can occur through splicing or microprocessor cleavage. The cytoplasmic component of miRNA maturation involves Dicer, which cleaves dsRNA to generate miRNA duplexes. The RISC assembly model involves the loading of miRNA into Ago2, with the passenger strand being cleaved to release the mature miRNA. RISC assembly and activation have been studied in Drosophila, with the model proposing ATP-dependent unwinding of the duplexes to load the mature miRNAMicroRNAs (miRNAs) are small, highly conserved non-coding RNA molecules that regulate gene expression. They are transcribed by RNA polymerases II and III, generating precursors that undergo cleavage to form mature miRNAs. The conventional biogenesis pathway involves two cleavage events, one in the nucleus and one in the cytoplasm. Alternative pathways exist, differing in the number of cleavage events and enzymes involved. The sorting of miRNA precursors to different pathways is determined by their origin, sequence, and thermodynamic stability. MiRNAs function through the RNA-induced silencing complex (RISC), which targets messenger RNA (mRNA) for silencing via mRNA cleavage or translation inhibition. Recent evidence indicates that P-bodies are essential for miRNA-mediated gene silencing, with RISC assembly and silencing occurring primarily within P-bodies. The P-body model outlines miRNA sorting and shuttling between specialized compartments that house enzymes required for slicer-dependent and -independent silencing. MiRNAs are found in most eukaryotes, including humans, and regulate at least 30% of protein-coding genes. They are involved in diverse cellular and metabolic pathways and play a crucial role in gene expression regulation. MiRNA expression profiles are altered in specific tumors, suggesting their involvement in cancer development and other diseases. MiRNA expression profiling is clinically relevant to cancer diagnosis, progression, and outcome. MiRNAs are small, single-stranded, non-coding RNA molecules that bind to target mRNA to prevent protein production through two mechanisms. Mature miRNAs are generated through two-step cleavage of primary miRNA (pri-miRNA), which incorporates into the RISC complex. The level of complementarity between the miRNA and target mRNA determines the silencing mechanism, either cleavage of target mRNA or translation inhibition. MiRNA biogenesis involves nuclear and cytoplasmic cleavage events by Drosha and Dicer. The nuclear cleavage of pri-miRNA by the microprocessor complex generates pre-miRNA, which is exported to the cytoplasm for further processing by Dicer. MiRNA biogenesis is a two-step process involving nuclear and cytoplasmic cleavage events. Intergenic miRNAs are transcribed by RNA polymerase II or III, while coding-intronic miRNAs are transcribed by RNA polymerase II as part of the pre-mRNA. MiRNA excision can occur through splicing or microprocessor cleavage. The cytoplasmic component of miRNA maturation involves Dicer, which cleaves dsRNA to generate miRNA duplexes. The RISC assembly model involves the loading of miRNA into Ago2, with the passenger strand being cleaved to release the mature miRNA. RISC assembly and activation have been studied in Drosophila, with the model proposing ATP-dependent unwinding of the duplexes to load the mature miRNA
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