Allele-Specific Loss Of The Mir-15a/16-1 Cluster
Veronese A, Pepe F, Chiacchia J, et al.
Key Points:
- Investigators tried to discover novel mechanism of transcription of miR-15a/16-1 cluster, independent of DLEU2, its host gene
- They demonstrated that G to A single nucleotide polymorphism (SNP) rs115069827 prevents maturation of miR-15a by reducing DROSHA complex binding to pri-microRNA 15a/16-1
- miR-15a/16-1 cluster transcribed by 2 allele-specific mechanisms: driven by RNA Polymerase II and RNA Polymerase III
- Latter mechanism dominant within CLL cells with mono-allelic 13q14 deletion and high expression of ZAP70
- CLL patient samples carrying 13q14 deletions not encompassing miR-15a/16-1 locus showed high expression of ZAP70 and primiR regulation by RPIII, in presence of both alleles of miR-15a/16-1
- Investigators demonstrated that CLL cells carrying mono-allelic deletion of this region entails loss of primiR regulation by DLEU2 promoter.
Implications:
- Investigators highlight that regulation of expression of miR-15a/16-1 is critical event in CLL pathogenesis.
View the original abstract on the ASH website.
