Droshaindependent

Droshaindependent refers to microRNA biogenesis pathways in which maturation proceeds without the canonical Drosha-DGCR8–mediated cleavage step in the nucleus. In most animals, microRNAs are produced from primary transcripts that are first processed by Drosha to yield precursor miRNAs, which are then exported to the cytoplasm and further processed by Dicer. Droshaindependent pathways bypass this initial nuclear processing, contributing to diversity in miRNA production and regulation.

The best-characterized Droshaindependent route is the mirtron pathway. Mirtrons are short introns that, after splicing and debranching, fold into hairpin structures resembling pre-miRNAs. These hairpins are then exported and cleaved by Dicer to form mature miRNAs, effectively linking splicing or RNA processing directly to mature miRNA generation without Drosha involvement. This pathway can integrate with tissue-specific or developmentally regulated splicing programs, providing an alternative source of regulatory small RNAs.

Other Droshaindependent routes include noncanonical pathways in which maturation can proceed without Drosha processing and, in some cases, without Dicer involvement, relying instead on alternative nucleases or Argonaute-family proteins for maturation steps. While less common than mirtrons, these routes demonstrate the plasticity of small RNA biogenesis and the capacity of cells to generate functional miRNAs under conditions where Drosha activity is limited or altered.

Significance lies in the expanded potential for gene regulation, context-dependent expression, and resilience of miRNA networks. Droshaindependent pathways underscore the complexity of miRNA biogenesis and their relevance to development, tissue specificity, and disease states.