hY3 RNA binds and inhibits Ribosomes and modulates the Starvation-induced Integrated Stress Response

Within this framework, translational control provides a rapid and efficient layer of regulation. Non-coding RNAs have recently emerged as effective modulators of translation, partly by targeting the ribosome.

The contribution of ribosome-associated non-coding RNAs (rancRNAs) to translation regulation, however, remains largely unexplored in human cells. Here, we identify the human Y3 RNA (hY3) as a rancRNA that inhibits protein synthesis and attenuates cellular metabolism. hY3 function is particularly critical under nutrient deprivation, where it promotes adaptive stress responses. In this context, depletion of hY3 disrupts the delicate balance between survival and apoptosis by reducing the expression of pro-survival factors and impairing activation of the integrated stress response (ISR).