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. 2020 Jul 4;10(7):999. doi: 10.3390/biom10070999

Table 1.

Features and requirements of UPF1-mediated RNA decay pathways.

UMD RNA Target NMD Effectors Translation Termination Selected Other Effectors 1 UPF1 Functions UPF1 Phosphorylation (p)-UPF1 Binding Factor
ATPase Helicase
NMD mRNAs, (lncRNAs; snoRNA hosts) UPF1+ (in variable combinations):
UPF2, UPF3A, UPF3B, SMG1c, SMG6, SMG5/7
yes EJC, Mov10, DHX34, SRSF1, NBAS, long 3′UTR
decapping and deadenylation factors, 3–5′ and 5′–3′ exonucleases, PNRC2
yes yes yes RNA?
SMD mRNA UPF1, UPF2, SMG1 yes STAU1, STAU2, dsRNA structures, PNRC2 yes yes yes UPF2 (STAU)
HMD Histone mRNA UPF1, SMG1 yes RNA stem loop
SLBP, ATR, DNA–PK, 3‘hExo, PNRC2
yes yes yes 3′UTR of histone mRNAs
RMD Proinflammatory cytokine transcripts UPF1, SMG1 yes Stem loop, with Py–Pu-Py-loop,
regnase-1
yes yes yes regnase-1
SRD mRNAs, circular RNAs UPF1 yes GRBP1 yes yes n.d. Structured RNA
TRIM71-MD CDKN1A/p21 mRNA UPF1, SMG1, SMG7 n.d. TRIM71, TRIM71-binding stem loop in 3′UTR n.d. n.d. implied 2 TRIM71?
GC-rich 3′UTR-MD mRNAs with GC-rich 3′UTRs UPF1, UPF2, SMG1 n.d. n.d. implied implied implied GC-rich mRNA
UPF1/SMG7/miRNA-MD mRNAs with CUG sequences embedded in miRNA seed sequences in 3′UTR UPF1, SMG7, n.d. miRNA loaded AGO, NOT1, NOT3 n.d. no n.d. CUG embedded in 7mer miRNA seed sequence
TumiD miRNA UPF1 no Tudor staphylococcal/ micrococcal-like nuclease (TSN), AGO2, GW182 n.d. yes No (by implication 2) TSN
GMD mRNA with GR-binding site often in 5′UTR UPF1 no glucocorticoid, glucocorticoid receptor (GR), ATM, PNRC2, DCP1A, YBX1, HRSP12 yes yes yes GR-PNRC2 complex
ER NMD ER-localized mRNAs UPF1
(others?)
n.d. NBAS, SEC61β n.d. n.d. No (by implication) NBAS

1 This list represents a selection of effectors as reported in the literature discussed in the text without claim to be exhaustive. 2 “implied” or “by implication“ indicates that the respective UPF1 function or feature was not tested directly but concluded upon by using UPF1 variants with mutations that interfere with these functions. N.d.: not determined.