Pregled bibliografske jedinice broj: 818416
Cryptic splicing events in the iron transporter ABCB7 and other key target genes in SF3B1 mutant myelodysplastic syndromes
Cryptic splicing events in the iron transporter ABCB7 and other key target genes in SF3B1 mutant myelodysplastic syndromes // Leukemia, 30 (2016), 2322-2331 (podatak o recenziji nije dostupan, članak, znanstveni)
CROSBI ID: 818416 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
Cryptic splicing events in the iron transporter
ABCB7 and other key target genes in SF3B1 mutant
myelodysplastic syndromes
Autori
Dolatshad, Hamid ; Pellagatti, Andrea ; Liberante, Fabio ; Llorian, M ; Repapi, Emmanouela ; Steeples, Violetta ; Roy, Swagata ; Scifo, Laura ; Armstrong, Richard N ; Shaw Jacqueline ; Yip, Bon Ham ; Killick, S ; Kušec, Rajko ; Taylor, Stephen ; Mills, Ken ; Savage, Kienan ; Smith, Chris WJ ; Boultwood, Jacqueline.
Izvornik
Leukemia (0887-6924) 30
(2016);
2322-2331
Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni
Ključne riječi
MDS SF3B1 mutant ; ring sideroblasts ; ABCB7 splicing
Sažetak
The splicing factor SF3B1 is the most frequently mutated gene in the myelodysplastic syndromes (MDS), and is strongly associated with the presence of ring sideroblasts (RS). We have performed a systematic analysis of cryptic splicing abnormalities from RNA-sequencing data on hematopoietic stem cells (HSCs) of SF3B1-mutant MDS cases with RS. Aberrant splicing events in many downstream target genes were identified and cryptic 3’ splice site usage was a frequent event in SF3B1-mutant MDS. The iron transporter ABCB7 is a wellrecognized candidate gene showing marked downregulation in MDS with RS. Our analysis unveiled aberrant ABCB7 splicing, due to usage of an alternative 3’ splice site in MDS patient samples, giving rise to a premature termination codon in the ABCB7 mRNA. Treatment of cultured SF3B1-mutant MDS erythroblasts and a CRISPR/Cas9- generated SF3B1-mutant cell line with the nonsense-mediated decay (NMD) inhibitor cycloheximide, showed that the aberrantly spliced ABCB7 transcript is targeted by NMD. We describe cryptic splicing events in the HSCs of SF3B1- mutant MDS, and our data support a model in which NMD-induced downregulation of the iron exporter ABCB7 mRNA transcript resulting from aberrant splicing caused by mutant SF3B1 underlies the increased mitochondrial iron accumulation found in MDS patients with RS.
Izvorni jezik
Engleski
Znanstvena područja
Temeljne medicinske znanosti
POVEZANOST RADA
Ustanove:
Medicinski fakultet, Zagreb,
Klinička bolnica "Dubrava"
Profili:
Rajko Kušec
(autor)
