**2.2 Non-canonical pathways for miRNA biosynthesis**

While most of the miRNAs are generated via the canonical pathway, there are many which are synthesized by the non-canonical pathways. Although there may be many such non-canonical miRNA synthesis pathways, they use up different combinations of proteins that are participants of the canonical pathway. Primarily, there are two types of the non-canonical pathways, the Drosha/DGCR8 independent route and the Dicer independent route. *Mitrons* are an example of miRNAs synthesized by the Drosha/DGCR8 independent pathway, where the pre-miRNAs

#### **Figure 1.**

*Biogenesis of miRNAs: A. transcription of pri-miRNA from the miRNA gene by RNA pol II followed by B. Drosha/DGCR8 cleavage of the pri-miRNA to pre-miRNA. C. the pre-miRNA is then exported from the nucleus to the cytoplasm with the help of the Exportin 5 /ran GTP complex where D. dicer cleavage of the hairpin structure takes place. E. One of the strands of the miRNA duplex is loaded onto the RISC, via the ago protein which causes the F. repression of the gene expression by base complementarity-induced mRNA degradation or translation repression.*

generated are similar to the Dicer substrates [20]. Here, Exponin-1 needs to transport the miRNA transcripts to the cytosol without Drosha processing it and allows a biased 3p strand loading onto Ago-2. On the other hand, the Dicer-independent pathway involves Drosha processing of the short hairpin RNA (shRNA) transcripts, but is too short to be cleaved by Dicer [21]. Hence, the entire pre-miRNA is loaded onto the Ago-2, which slices the 3p strand. Finally, the trimming from 3′-5′ of the 5p strand concludes the maturation of the miRNA [14, 22].
