Indian Journal of Biochemistry & Biophysics Vol. 50, June 2013, pp. 169-176 Promoters, toll like receptors and microRNAs: A strange association Kalyani Korla a , Patrizio Arrigo b and Chanchal K Mitra a* a School of Life Sciences, University of Hyderabad, Hyderabad, India b Institute of Macromolecular Studies, via De Marini 6 16149, Genoa, Italy Received 20 December 2012; revised 10 April 2013 Toll-like receptors (TLRs) are proteins that play key role in the innate immune system. In the present study, ~1000 base pairs upstream are taken from the transcription start site of the various TLR genes (10 known) in human. About 40 microRNAs have been identified that share 12-19 nucleotide sequence similarity with the promoter regions of 10 TLRs. It is proposed that the microRNA performs potential role in identification of promoter sequence and initiation of transcription. Keywords: Toll like receptor, miRNA, Promoter, microRNA, Transcription Transcription starts with the binding of transcription factor to the promoter region present in the upstream of transcription start site (TSS). Promoter recognition plays a crucial role in the transcription of genes in both eukaryotes and prokaryotes. There are consensus sequences as TATAAT and TTGACA in prokaryotes, but there are no such universal conserved sequences for promoter recognition in eukaryotes 1 . Transcription factors are known to bind to a unique sequence in the promoter regions. Similarly, miRNA may recognize short unique sequences based on nucleic acid base complementarity. We suggest that miRNAs may have an important role in the recognition of the unique binding site for a transcription factor. miRNAs are small (~22 nt long) non-coding RNAs that are established as post-transcriptional gene regulators in cytoplasm by targeting mRNAs and leading to their specific degradation or by repressing their translation. It has been demonstrated that if there is complete complementation between the miRNA and target mRNA sequence, the mRNA is cleaved, leading to direct mRNA degradation 2 . Since they affect gene regulation, they are involved in most of the biological processes, such as cell differentiation, cell proliferation, embryonic development and apoptosis. Individual miRNAs can repress large sets of mRNAs that are not required at a particular developmental stage 3 . miRNAs can also control the expression of critical transcriptional regulators 4,5 . However, transcription factors are essential components and are expected to be readily available at a basal level. Computational studies indicate that approximately 30% of protein coding genes are regulated by miRNAs and each miRNA could target a number of genes 6 . However, the identification of target mRNA of various miRNAs and the underlying mechanism is still widely unexplored. miRNA genes are transcribed to give rise to primary miRNA (pri-miRNA) transcripts. These are processed in the nucleus by Drosha, an RNase III endonuclease, to form hairpin structured precursor miRNA (pre-miRNA). These pre-miRNAs are transported to the cytoplasm by Exportin 5 and then cleaved by Dicer to form mature miRNAs. These mature miRNAs in the cytoplasm are responsible for RNA silencing. Recent studies show that many miRNAs reside inside the nucleus 7 . Some of them are highly enriched in the nucleus. It has been reported that some miRNAs are imported to nucleus through a process directed by a hexanucleotide sequence present in miRNA 8 . miRNA and pre-miRNA are found to induce gene expression by targeting promoter sequences in a sequences-specific manner 9 . miRNA may also direct epigenetic gene silencing pathway in the nucleus 10 . The role of miRNA in transcriptional gene regulation is little studied, but the studies indicate both activating and silencing effects of miRNA 9,10 . The presence of transcription factor binding site in the pre-miRNAs is thought to regulate transcription of the pri-miRNA gene transcript 11 . But, this finding —————— *Author for correspondence E-mail: c_mitra@yahoo.com Fax: +91 40 2301 0120 Tel: +91 40 2313 4668