Precision in RNA degradation: helicases, ribosome and RNA polymerase stalling, and RNA modifications

Errors in transcription and RNA processing generate aberrant transcripts that can produce truncated, nonfunctional, or dominant-negative proteins. RNA surveillance pathways, centered on the RNA exosome, recognize diverse processing defects and initiate targeted RNA degradation. These mechanisms also regulate the short half-life of chromatin-associated noncoding RNAs through co- and/or post-transcriptional degradation. This review examines how the RNA exosome achieves substrate specificity, focusing on its interactions with the helicase cofactors mRNA transport 4 (MTR4) and superkiller 2 (SKIV2L) and the modulatory role of RNA modifications such as N⁶-methyladenosine. The broad spectrum of RNA exosome targets underscores its central functions in transcription, translation, genome integrity, and cell fate determination.