A great body of work has focused on understanding the role that gene regulation at the transcriptional level plays in blood cell production and diseases that disrupt this process. However, until recently there has been limited insight on the role that post-transcriptional gene regulation has in both normal and pathological disorders of human hematopoiesis. Specifically, the regulation of messenger RNA translation can have a significant impact upon gene expression, and how this process affects hematopoiesis has only been explored in limited studies. In this talk, the role of ribosomal protein gene mutations in the specific disorder of red blood cell production, Diamond-Blackfan anemia, will be discussed. Recent findings from our laboratory show that mutations in the key hematopoietic transcription factor gene, GATA1, can result in Diamond-Blackfan anemia in rare cases. We have gone on to show that more common mutations in ribosomal protein genes can disrupt translation of GATA1 and thereby suggest a common underlying mechanism for the impaired erythropoiesis observed in Diamond-Blackfan anemia. We discuss both the mechanistic underpinnings of our observations and how these findings have important therapeutic implications. Other recent examples of how disordered translation can impair human hematopoiesis will also be examined. This talk will provide a cohesive framework to understand the implications of these recent findings for both normal and disordered human hematopoiesis.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
