Diverse miRNA maturation pathways in animals. miRNA genes are transcribed by RNA-polymerase II or III into long transcripts termed pri-miRNA. In the major miRNA maturation pathway (solid arrows), a pri-miRNA is cleaved into an intermediate called pre-miRNA by Drosha, an RNase III protein, along with its RNA-binding partner DGCR8. The pre-miRNA, ~ 70 nucleotides in length, is exported by exportin-5 into the cytoplasm, where it is further cleaved by another RNase III enzyme Dicer to yield a miRNA duplex. The miRNA duplex is incorporated into the effector complex RISC and unwound into a mature single strand. The mature miRNA leads to translational repression or mRNA degradation, depending on the complementary to the target mRNAs. Alternative processing pathways have been uncovered (dashed arrows). A class of miRNAs, called mirtrons, is bracketed by splice site sequences. They are processed into pre-miRNAs by the spliceosome and the debranching enzyme. The A-to-I modification of pri-miRNAs and/or pre-miRNAs by the adenosine deaminase ADAR may block their cleavage by Drosha or Dicer, or alter the specificity of the miRNAs. The non-processable RNA species get degraded by nucleases, e.g. Tudor-SN in the cytoplasm.