Published on June 4, 2020 in Blood volume 135(23).

PubMed ID: 32097467

DOI: S0006-4971(20)61978-4

Abstract:

Noncoding RNAs, including small nucleolar RNAs (snoRNAs), play important roles inleukemogenesis, but the relevant mechanisms remain incompletely understood. Weperformed snoRNA-focused CRISPR-Cas9 knockout library screenings that targeted theentire snoRNAnome and corresponding host genes. The C/D box containing SNORD42A wasidentified as an essential modulator for acute myeloid leukemia (AML) cell survivaland proliferation in multiple human leukemia cell lines. In line, SNORD42A wasconsistently expressed at higher levels in primary AML patient samples than in CD34+progenitors, monocytes, and granulocytes. Functionally, knockout of SNORD42A reducedcolony formation capability and inhibited proliferation. The SNORD42A acts as a C/Dbox snoRNA and directs 2'-O-methylation at uridine 116 of 18S ribosomal RNA (rRNA).Deletion of SNORD42A decreased 18S-U116 2'-O-methylation, which was associated witha specific decrease in the translation of ribosomal proteins. In line, the cell sizeof SNORD42A deletion carrying leukemia cells was decreased. Taken together, thesefindings establish that high-level expression of SNORD42A with concomitant U116 18SrRNA 2'-O-methylation is essential for leukemia cell growth and survival.CI - © 2020 by The American Society of Hematology.