3' end mRNA processing: molecular mechanisms and implications for health and disease.
Recent advances in the understanding of the molecular mechanism of mRNA 3' end processing have uncovered a previously unanticipated integrated network of transcriptional and RNA-processing mechanisms. A variety of human diseases impressively reflect the importance of the precision of the complex 3' end-processing machinery and gene specific deregulation of 3' end processing can result from mutations of RNA sequence elements that bind key specific processing factors. Interestingly, more general deregulation of 3' end processing can be caused either by mutations of these processing factors or by the disturbance of the well-coordinated equilibrium between these factors. From a medical perspective, both loss of function and gain of function can be functionally relevant, and an increasing number of different disease entities exemplifies that inappropriate 3' end formation of human mRNAs can have a tremendous impact on health and disease. Here, we review the mechanistic hallmarks of mRNA 3' end processing, highlight the medical relevance of deregulation of this important step of mRNA maturation and illustrate the implications for diagnostic and therapeutic strategies.
Danckwardt
Sven
S
Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany.
Hentze
Matthias W
MW
Kulozik
Andreas E
AE
D000818:Animals; D006801:Humans; D007109:Immunity / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D009369:Neoplasms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D026721:RNA 3' End Processing / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology
D012333:RNA, Messenger