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- Investigation Of The Role Of Microrna- 223, Microrna -381 And Microrna- 505 In The Regulation Of Transcription Factor Nfi-A.

Introduction

It has been shown that the brain‘s tolerance to ischaemic injuries can be temporarily augmented when exposed to a non-injurious pre-conditioning stimulus (Gidday, 2006). The transcription factor NFI-A, a CCAAT-related binding protein that functions both in viral DNA replication and in the regulation of gene expression was found to be a gene that was upregulated during this phenomenon. It has also been shown to play a role in preconditioning-induced neuroprotective functions (Zheng et al, submitted).
Experiments have indicated that human NFIA is negatively controlled by miR-223, in that its translation is repressed by the binding of micro RNA 223 to a binding site on the 3’ UTR of the gene. (Fazi et al,2005).
MicroRNAs (miRNAs) are endogenously encoded, 22 nucleotide small noncoding RNAs that have been found to direct sequence specific down regulation by mRNA cleavage, cleavage-independent mRNA degradation or translational suppression of mRNA. (Pillai,2005 ; Valencia-Sanchez et al, 2006).
They have been found to induce post-transcriptional gene silencing through base pairing with their target mRNAs.(Bartel, 2004 ; Kim, 2005. The binding of miRNAs to complementary sequences in the 3’ UTRs of mRNAs appears to direct translational suppression.
Targets of microRNAs in many cases only require a continuous 6 base pair ‘seed match’ to be appropriately effective. This would result in the potential coordination of the regulation of hundreds of genes. Genomic analyses have shown that one third of human genes could be miRNA targets. (Lewis et al. 2005).
This offers a potential method to control the expression of NFIA and thus indirectly, cell survival.
Hypothesis

The translational inhibition of mRNAs is dependent on the binding of micro RNAs to target sequences in the 3’UTR of these mRNAs. Prominent binding sites for miR-505 and miR-381 and miR-223 have been identified on the far end of the human NFIA 3’ UTR. This in turn indicates likely...