miRNAs, the small but mighty inhibitors of complementary mRNA sequences, might be accused of having a Napoleon complex, but they don’t start out life itty-bitty—they are transcribed as long primary miRNAs (pri-miRNAs).
Cleavage by the RNase III-like enzyme Drosha in the nucleus releases a ~70-nt stem-loop structure (pre-mRNA), which is further processed by Dicer in the cytoplasm to mature, ~21−23-nt miRNA. Until now, the exact timing and location of pri-miRNA’s makeover to pre-miRNA were unknown.
A recent paper by Jan Pawlicki and Joan Steitz at Yale revealed that Drosha processes pri-miRNAs co-transcriptionally. Pri-miRNA transcripts that were engineered to be retained at transcription sites or that had flanking exons were processed more efficiently to pre-miRNAs than pri-mRNAs that were polyadenylated and released.
In contrast, overexpressed miRNAs that were processed inefficiently at the site of transcription accumulated in non-functional nuclear foci. According to Steitz, “Our results argue that miRNA biogenesis—which is perturbed in many disease states—is regulated by mechanisms linked to transcription.” For more details, check out Journal of Cell Biology, July 2008