This is part of an original proposal I came up with for one of my courses. I will be following up on it soon with another project and hopefully get some answers some day :D
This article will be posted in parts. Today, I will be giving an introduction to miRNAs.
MicroRNAs are small (~22nucleotide long) non-coding RNAs that form part of a highly conserved system of RNA-based gene regulation in eukaryotes. Mature miRNAs are found in cytoplasm where they act as post transcriptional regulators of gene expression by base-pairing with target mRNAs.
miRNAs are transcribed as regions of longer RNA molecules, that are processed in the nucleus into hairpin RNAs (70-100nt) by the dsRNA-specific ribonuclease Drosha. The hairpin RNAs are transported to the cytoplasm via an exportin-5 dependent mechanism where they are digested by a second dsRNA specific ribonuclease called Dicer. The resulting ~22mer is bound to a complex called RNA-induced Silencing Complex (RISC). RISC is responsible for RNAi. These miRNAs bind to mRNA through limited complementarity in humans and thus, cause reduced/blocked gene expression, through mechanisms not yet understood completely. miRNAs are bound to proteins that belong to the Argonaute family and, in humans, may also assemble with other proteins, including the Gemin3 and Gemin4 proteins, to form micro-ribonucleoprotein complexes[1]
The first miRNAs, lin-4 were discovered in Caenorhabditis elegans in 1993 (Lee et al. 1993) in a genetic focused on identifying genes involved in the heterochronic pathway. For almost a decade, they were considered relatively unimportant. But they have stirred much enthusiasm in the biological and medical communities since 2004 when their function of stifling the production of proteins , contrary to their close relatives, mRNA was highlighted through the work of many laboratories and their roles in brain development, HIV resistance, blood cell development, obstruction of genes causing certain types of cancer etc. were discovered.
References:
1. 9. Kiriakidou M, Nelson PT, Kouranov A, et al; A combined computational-experimental approach predicts human microRNA targets. Genes Dev. 2004 May 15;18(10):1165-78
This article will be posted in parts. Today, I will be giving an introduction to miRNAs.
MicroRNAs are small (~22nucleotide long) non-coding RNAs that form part of a highly conserved system of RNA-based gene regulation in eukaryotes. Mature miRNAs are found in cytoplasm where they act as post transcriptional regulators of gene expression by base-pairing with target mRNAs.
miRNAs are transcribed as regions of longer RNA molecules, that are processed in the nucleus into hairpin RNAs (70-100nt) by the dsRNA-specific ribonuclease Drosha. The hairpin RNAs are transported to the cytoplasm via an exportin-5 dependent mechanism where they are digested by a second dsRNA specific ribonuclease called Dicer. The resulting ~22mer is bound to a complex called RNA-induced Silencing Complex (RISC). RISC is responsible for RNAi. These miRNAs bind to mRNA through limited complementarity in humans and thus, cause reduced/blocked gene expression, through mechanisms not yet understood completely. miRNAs are bound to proteins that belong to the Argonaute family and, in humans, may also assemble with other proteins, including the Gemin3 and Gemin4 proteins, to form micro-ribonucleoprotein complexes[1]
The first miRNAs, lin-4 were discovered in Caenorhabditis elegans in 1993 (Lee et al. 1993) in a genetic focused on identifying genes involved in the heterochronic pathway. For almost a decade, they were considered relatively unimportant. But they have stirred much enthusiasm in the biological and medical communities since 2004 when their function of stifling the production of proteins , contrary to their close relatives, mRNA was highlighted through the work of many laboratories and their roles in brain development, HIV resistance, blood cell development, obstruction of genes causing certain types of cancer etc. were discovered.
References:
1. 9. Kiriakidou M, Nelson PT, Kouranov A, et al; A combined computational-experimental approach predicts human microRNA targets. Genes Dev. 2004 May 15;18(10):1165-78
Fig. Biogenesis of miRNAs
from http://www.gurdon.cam.ac.uk/~miskalab/research.php
from http://www.gurdon.cam.ac.uk/~miskalab/research.php
