Stress granules and RNA modifications in blood development and erythroid regeneration

Stress granules (SGs) are RNA and protein assemblies that form rapidly in the cytoplasm in response to cellular or environmental stress. SGs, traditionally recognized as transient repressors of translation, are now understood as versatile regulatory centers that shape RNA metabolism, signaling, proteostasis, and cell fate. In this review, we collate recent findings showing SGs' role in steady-state and regenerative stress in erythropoiesis.

Blood loss, anemia caused by ribosomal mutations, has been reported to alter the SG axis and protein translation. During regeneration stress, SGs selectively capture lineage-defining RNAs to regulate their translation during recovery phases. This process ensures that blood progenitors and differentiating cells retain essential transcripts, supporting proper fate decisions and regeneration. Pathological SG accumulation disrupts RNA metabolism and translational reprogramming, key to blood cell regeneration.

SGs regulate the transcriptome to endure stress via translational control mechanisms during erythropoiesis. SG deregulation can undermine these adaptive processes. Therapies modulating SG formation, dissolving pathological SGs, or influencing RNA sorting via genetics or targeted small molecules promise new directions to restore blood health, treat anemia, and regeneration in a range of blood disorders.