An endogenous cluster of target-directed microRNA degradation sites induces decay of distinct microRNA families.

While much is known about miRNA biogenesis and canonical miRNA targeting, relatively less is understood about miRNA decay. The major miRNA decay pathway in metazoans is mediated through target-directed miRNA degradation (TDMD), in which certain RNAs can 'trigger' miRNA decay. All known triggers for TDMD base pair with the miRNA seed, and extensively base pair on the miRNA 3 prime end, a pattern that supposedly induces a TDMD-competent conformational change of Argonaute (Ago), allowing for miRNA turnover.

Target-directed microRNA degradation: Mechanisms, significance, and functional implications.

MicroRNAs (miRNAs) are small non-coding RNAs that play a fundamental role in enabling miRNA-mediated target repression, a post-transcriptional gene regulatory mechanism preserved across metazoans. Loss of certain animal miRNA genes can lead to developmental abnormalities, disease, and various degrees of embryonic lethality. These short RNAs normally guide Argonaute (AGO) proteins to target RNAs, which are in turn translationally repressed and destabilized, silencing the target to fine-tune gene expression and maintain cellular homeostasis.

N-methyladenosine in 7SK small nuclear RNA underlies RNA polymerase II transcription regulation.

N-methyladenosine (mA) modifications play crucial roles in RNA metabolism. How mA regulates RNA polymerase II (RNA Pol II) transcription remains unclear. We find that 7SK small nuclear RNA (snRNA), a regulator of RNA Pol II promoter-proximal pausing, is highly mA-modified in non-small cell lung cancer (NSCLC) cells.