# The role of distinct APOBEC/ADAR mRNA levels in mutational signatures linked to aging and ultraviolet radiation **Authors:** Ahmadreza Niavarani PMC · DOI: 10.1038/s41598-024-64986-6 · Scientific Reports · 2024-07-04 ## TL;DR This study explores how APOBEC and ADAR mRNA levels influence mutational signatures related to aging and UV radiation in cancer. ## Contribution The study identifies novel links between specific APOBEC/ADAR mRNA levels and distinct mutational signatures in cancer. ## Key findings - APOBEC1 mRNA levels are linked to aging-related mutational signatures like SBS17b and SBS18. - ADARB1 mRNA levels are associated with UV radiation-related signatures such as SBS7a-d and DBS1. - APOBEC3A/APOBEC3B mRNA levels influence SBS3 and SBS16 mutational signatures. ## Abstract The APOBEC/AID family is known for its mutator activity, and recent evidence also supports the potential impact of ADARs. Furthermore, the mutator impacts of APOBEC/ADAR mutations have not yet been investigated. Assessment of pancancer TCGA exomes identified enriched somatic variants among exomes with nonsynonymous APOBEC1, APOBEC3B, APOBEC3C, ADAR, and ADARB1 mutations, compared to exomes with synonymous ones. Principal component (PC) analysis reduced the number of potential players to eight in cancer exomes/genomes, and to five in cancer types. Multivariate regression analysis was used to assess the impact of the PCs on each COSMIC mutational signature among pancancer exomes/genomes and particular cancers, identifying several novel links, including SBS17b, SBS18, and ID7 mainly determined by APOBEC1 mRNA levels; SBS40, ID1, and ID2 by age; SBS3 and SBS16 by APOBEC3A/APOBEC3B mRNA levels; ID5 and DBS9 by DNA repair/replication (DRR) defects; and SBS7a-d, SBS38, ID4, ID8, ID13, and DBS1 by ultraviolet (UV) radiation/ADARB1 mRNA levels. APOBEC/ADAR mutations appeared to potentiate the impact of DRR defects on several mutational signatures, and some factors seemed to inversely affect certain signatures. These findings potentially implicate certain APOBEC/ADAR mutations/mRNA levels in distinct mutational signatures, particularly APOBEC1 mRNA levels in aging-related signatures and ADARB1 mRNA levels in UV radiation-related signatures. ## Linked entities - **Genes:** APOBEC1 (apolipoprotein B mRNA editing enzyme catalytic subunit 1) [NCBI Gene 339], APOBEC3B (apolipoprotein B mRNA editing enzyme catalytic subunit 3B) [NCBI Gene 9582], APOBEC3C (apolipoprotein B mRNA editing enzyme catalytic subunit 3C) [NCBI Gene 27350], ADAR (adenosine deaminase RNA specific) [NCBI Gene 103], ADARB1 (adenosine deaminase RNA specific B1) [NCBI Gene 104], APOBEC3A (apolipoprotein B mRNA editing enzyme catalytic subunit 3A) [NCBI Gene 200315] ## Full-text entities - **Genes:** ID1 (inhibitor of DNA binding 1) [NCBI Gene 3397] {aka ID, bHLHb24}, ID4 (inhibitor of DNA binding 4) [NCBI Gene 3400] {aka IDB4, bHLHb27}, APOBEC3B (apolipoprotein B mRNA editing enzyme catalytic subunit 3B) [NCBI Gene 9582] {aka A3B, APOBEC1L, ARCD3, ARP4, DJ742C19.2, PHRBNL}, ADAR (adenosine deaminase RNA specific) [NCBI Gene 103] {aka ADAR1, AGS6, DRADA, DSH, DSRAD, G1P1}, APOBEC1 (apolipoprotein B mRNA editing enzyme catalytic subunit 1) [NCBI Gene 339] {aka APO1, APOBEC-1, BEDP, CDAR1, HEPR}, AICDA (activation induced cytidine deaminase) [NCBI Gene 57379] {aka AID, ARP2, CDA2, HEL-S-284, HIGM2}, APOBEC3A (apolipoprotein B mRNA editing enzyme catalytic subunit 3A) [NCBI Gene 200315] {aka A3A, ARP3, PHRBN, bK150C2.1}, ID2 (inhibitor of DNA binding 2) [NCBI Gene 3398] {aka GIG8, ID2A, ID2H, bHLHb26}, ADARB1 (adenosine deaminase RNA specific B1) [NCBI Gene 104] {aka ADAR2, DRABA2, DRADA2, NEDHYMS, RED1}, APOBEC3C (apolipoprotein B mRNA editing enzyme catalytic subunit 3C) [NCBI Gene 27350] {aka A3C, APOBEC1L, ARDC2, ARDC4, ARP5, PBI} - **Diseases:** cancer (MESH:D009369), DNA repair/replication (DRR) (MESH:D049914) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC11224270/full.md ## Figures 6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11224270/full.md ## References 63 references — full list in the complete paper: https://tomesphere.com/paper/PMC11224270/full.md --- Source: https://tomesphere.com/paper/PMC11224270