TABLE 2.
Nm in disease
| Genes | Nm-related functions | Diseases | Disease association |
|---|---|---|---|
| Nm writers/guides | |||
| FBL | 2′-O-methyltransferase component of box C/D snoRNP | Cancer | Overexpressed in cancer, correlates with poor prognosis |
| Multiple snoRNAs | Guide Nm modifications on multiple targets, including rRNA and pri-miRNA | Cancer | Dysregulated in cancer (often overexpressed), promote tumorigenesis, correlate with prognosis |
| Rpl13a-encoded snoRNAs | Box C/D snoRNAs, guide Nm modifications in 28S and 18S rRNAs | Cardiometabolic disease | Propagate oxidative stress, promote glucose resistance, promote atherosclerosis |
| Multiple scaRNAs | Guide Nm modifications on U2 and U6 snRNAs | Tetralogy of Fallot | Multiple scaRNAs that guide Nm on U2 and U6 snRNAs are differentially expressed in TOF |
| Snord115, Snord116 | Box C/D snoRNAs, target Nm site(s) unknown | Prader–Willi syndrome | PWS is caused by paternal loss of imprinted genes in 15q11–q13 locus, which has many copies of Snord115 and Snord116 |
| FTSJ1 | Deposits Nm32 and Nm34 in anticodon loop of phenylalanine, tryptophan, and leucine tRNAs | NSXLID | Loss of function of FTSJ1, including missense mutation causing lack of Nm34 only, causes NSXLID |
| Factors that associate with Nm writers | |||
| NPM1 | Ribosome biogenesis factor that binds box C/D snoRNAs | AML, dyskeratosis congenita | NPM1 mutations are common in AML |
| AES | Required for interaction of RNA helicase DDX21 with box C/D snoRNPs; impacts box C/D snoRNA levels and rRNA Nm | AML | AES levels are increased in AML1–ETO (also called RUNX1–RUNX1T1) fusion positive AML |
| LARP7 | Promotes Nm on U6 snRNA by facilitating interaction of box C/D snoRNAs with U6 snRNA | Alazami syndrome | Loss of LARP7 causes Alazami syndrome |
| FMR1 (FMRP) | Binds box C/D snoRNAs and impacts rRNA Nm; selectively binds BC1 noncoding RNAs without Nm | FXS | FXS is caused by expanded CGG repeats in FMR1 |
| TARDBP (TDP43) | Promotes Nm on U1 and U2 snRNAs by promoting scaRNA localization to Cajal bodies | ALS, FTLD | TDP43 inclusions are a pathologic hallmark in ALS and FTLD-U |
| Factors that regulate expression of Nm writers | |||
| TP53 | Down-regulates FBL transcription, impacts rRNA Nm, decreases IRES-dependent translation | Cancer | TP53 is a tumor suppressor that is frequently mutated in cancer |
| MYC | Up-regulates FBL and certain box C/D snoRNAs, increases 18S Cm174 | Cancer | MYC is a proto-oncogene that is frequently mutated or overexpressed in cancer |
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(TOF) Tetralogy of Fallot; (PWS) Prader–Willi syndrome; (NSXLID) non-syndrome X-linked intellectual disability; (AML) acute myeloid leukemia; (DDX21) DExD-box helicase 21; (ALS) amyotrophic lateral sclerosis; (FTLD-U) frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions; (IRES) internal ribosome entry site. See text for corresponding references.
