# Non-AUG translation initiation in mammals **Authors:** Dmitry E. Andreev, Gary Loughran, Alla D. Fedorova, Maria S. Mikhaylova, Ivan N. Shatsky, Pavel V. Baranov PMC · DOI: 10.1186/s13059-022-02674-2 · Genome Biology · 2022-05-09 ## TL;DR This paper explores how proteins can be made from unexpected parts of RNA in mammals, challenging traditional views of how genes are read. ## Contribution The paper highlights the widespread role of non-AUG start codons in shaping mammalian proteomes. ## Key findings - Non-AUG initiation contributes significantly to proteome diversity in mammals. - Leaky scanning allows ribosomes to bypass inefficient start codons and initiate downstream. - Proteogenomic studies reveal translation beyond annotated coding regions. ## Abstract Recent proteogenomic studies revealed extensive translation outside of annotated protein coding regions, such as non-coding RNAs and untranslated regions of mRNAs. This non-canonical translation is largely due to start codon plurality within the same RNA. This plurality is often due to the failure of some scanning ribosomes to recognize potential start codons leading to initiation downstream—a process termed leaky scanning. Codons other than AUG (non-AUG) are particularly leaky due to their inefficiency. Here we discuss our current understanding of non-AUG initiation. We argue for a near-ubiquitous role of non-AUG initiation in shaping the dynamic composition of mammalian proteomes. The online version contains supplementary material available at 10.1186/s13059-022-02674-2. ## Full-text entities - **Genes:** EIF3A (eukaryotic translation initiation factor 3 subunit A) [NCBI Gene 8661] {aka EIF3, EIF3S10, P167, TIF32, eIF3-p170, eIF3-theta}, PRKAB1 (protein kinase AMP-activated non-catalytic subunit beta 1) [NCBI Gene 5564] {aka AMPK, HAMPKb}, DDX23 (DEAD-box helicase 23) [NCBI Gene 9416] {aka PRPF28, SNRNP100, U5-100K, U5-100KD, prp28}, ASNSD1 (asparagine synthetase domain containing 1) [NCBI Gene 54529] {aka NBLA00058, NS3TP1}, CIP2A (cellular inhibitor of PP2A) [NCBI Gene 57650] {aka KIAA1524, NOCIVA, p90}, HFM1 (helicase for meiosis 1) [NCBI Gene 164045] {aka MER3, POF9, SEC63D1, Si-11, Si-11-6, helicase}, MAPK13 (mitogen-activated protein kinase 13) [NCBI Gene 5603] {aka MAPK 13, MAPK-13, PRKM13, SAPK4, p38delta}, EIF5A (eukaryotic translation initiation factor 5A) [NCBI Gene 1984] {aka EIF-5A, EIF5A1, FABAS, eIF-4D, eIF5AI}, BZW1 (basic leucine zipper and W2 domains 1) [NCBI Gene 9689] {aka 5MP2, BZAP45, Nbla10236}, RAN (RAN, member RAS oncogene family) [NCBI Gene 5901] {aka ARA24, Gsp1, TC4}, MIEF1 (mitochondrial elongation factor 1) [NCBI Gene 54471] {aka D3A, HSU79252, MID51, OPA14, SMCR7L, dJ1104E15.3}, EEF2K (eukaryotic elongation factor 2 kinase) [NCBI Gene 29904] {aka CaMKIII, HSU93850, eEF-2K}, SLC35A4 (solute carrier family 35 member A4) [NCBI Gene 113829], msl-2 (male-specific lethal 2) [NCBI Gene 33565] {aka CG3241, Dmel\CG3241, MSL, MSL2, Msl 1-3, Msl2}, DHX36 (DEAH-box helicase 36) [NCBI Gene 170506] {aka DDX36, G4R1, MLEL1, RHAU}, EIF1B (eukaryotic translation initiation factor 1B) [NCBI Gene 10289] {aka GC20}, Sxl (Sex lethal) [NCBI Gene 3772180] {aka CG14425, CG18350, CG33070, CG43770, Dm-Sxl, DmSxl}, DHX9 (DExH-box helicase 9) [NCBI Gene 1660] {aka DDX9, LKP, MRD75, NDH2, NDHII, RHA}, EEF2 (eukaryotic translation elongation factor 2) [NCBI Gene 1938] {aka EEF-2, EF-2, EF2, SCA26}, BAG1 (BAG cochaperone 1) [NCBI Gene 573] {aka BAG-1, HAP, RAP46}, EIF5 (eukaryotic translation initiation factor 5) [NCBI Gene 1983] {aka EIF-5, EIF-5A}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, BZW2 (basic leucine zipper and W2 domains 2) [NCBI Gene 28969] {aka 5MP1, HSPC028, MST017, MSTP017}, HBB (hemoglobin subunit beta) [NCBI Gene 3043] {aka CD113t-C, ECYT6, beta-globin}, EIF1 (eukaryotic translation initiation factor 1) [NCBI Gene 10209] {aka A121, EIF-1, EIF1A, ISO1, SUI1}, MRPL18 (mitochondrial ribosomal protein L18) [NCBI Gene 29074] {aka HSPC071, L18mt, MRP-L18, uL18m}, FGF2 (fibroblast growth factor 2) [NCBI Gene 2247] {aka BFGF, FGF-2, FGFB, HBGF-2}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, RPS6KA1 (ribosomal protein S6 kinase A1) [NCBI Gene 6195] {aka HU-1, MAPKAPK1, MAPKAPK1A, RSK, RSK1, p90Rsk}, EIF4G2 (eukaryotic translation initiation factor 4 gamma 2) [NCBI Gene 1982] {aka AAG1, DAP5, NAT1, P97}, EIF4A2 (eukaryotic translation initiation factor 4A2) [NCBI Gene 1974] {aka BM-010, DDX2B, EIF4A, EIF4F, NEDHSS, eIF-4A-II}, POLG (DNA polymerase gamma, catalytic subunit) [NCBI Gene 5428] {aka MIRAS, MTDPS4A, MTDPS4B, PEO, POLG1, POLGA}, RPL18 (ribosomal protein L18) [NCBI Gene 6141] {aka DBA18, L18, eL18}, DED1 (DEAD-box ATP-dependent RNA helicase DED1) [NCBI Gene 854379] {aka SPP81}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, DDX3X (DEAD-box helicase 3 X-linked) [NCBI Gene 1654] {aka CAP-Rf, DBX, DDX14, DDX3, HLP2, MRX102}, MKKS (MKKS centrosomal shuttling protein) [NCBI Gene 8195] {aka BBS6, HMCS, KMS, MKS}, STXBP1 (syntaxin binding protein 1) [NCBI Gene 6812] {aka DEE4, MUNC18-1, N-Sec1, NSEC1, P67, RBSEC1}, PIK3CD (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta) [NCBI Gene 5293] {aka APDS, IMD14, IMD14A, IMD14B, P110DELTA, PI3K} - **Diseases:** cancer (MESH:D009369), OGD (MESH:D000860), neurodegenerative diseases (MESH:D019636), neurological disorders (MESH:D009461), Glucose (MESH:D018149) - **Species:** Bos taurus (bovine, species) [taxon 9913], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Homo sapiens (human, species) [taxon 9606], Ovis aries (domestic sheep, species) [taxon 9940], Drosophila melanogaster (fruit fly, species) [taxon 7227], Barley yellow dwarf virus (species) [taxon 12037] ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC9082881/full.md ## Figures 3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC9082881/full.md ## References 123 references — full list in the complete paper: https://tomesphere.com/paper/PMC9082881/full.md --- Source: https://tomesphere.com/paper/PMC9082881