Reagent/Resource	Reference or source	Identifier or catalog number
Experimental models
Normal Human Dermal Fibroblasts (NHDFs)	Lonza	CC‐2511
Antibodies
IE1/2, mouse monoclonal	Millipore	Mab810R
UL44, mouse monoclonal	Virus Sys	CA006
pp28, mouse monoclonal	Virus Sys	CA004‐100
PKR phospho (Thr446), rabbit monoclonal	Abcam	ab32036
PKR, rabbit polyclonal	Proteintech	18244‐1
MDA5, rabbit polyclonal	Proteintech	21775‐1‐AP
ISG15, rabbit polyclonal	Proteintech	15981‐1‐AP
Mx1, rabbit polyclonal	Proteintech	13750‐1‐AP
CNOT1, rabbit polyclonal	Proteintech	14276‐1‐AP
CNOT2, rabbti polyclonal	Novus	NBP2‐56034
CNOT3, rabbit polyclonal	Proteintech	11135‐1‐AP
CNOT7, rabbit monclonal	Abcam	ab195587
VACV, rabbit polyclonal	Virostat	8101
ICP4, mouse monoclonal	Abcam	ab6514
US3	Gift of B. Roizman
gC, mouse monoclonal	Abcam	ab6509
GAPDH, rabbit monoclonal	Cell Signaling	2118
Tubulin (beta), rabbit monoclonal	Cell Signaling	2128
Anti‐mouse AlexaFluor 647	Fisher Scientific	A32787
Anti‐mouse HRP	Fisher Scientific	45‐000‐679
Anti‐rabbit HRP	Fisher Scientific	NA934
Oligonucleotides and sequence‐based reagents
RT‐QPCR PRIMERS:
GAPDH‐F	TCTTTTGCGTCGCCAGCCGA
GAPDH‐R	ACCAGGCGCCCAATACGACC
PARN‐F	CGCAACAATAGTTTTACAGC
PARN‐R	AGAAAGCTCCTTCTTCATTC
PAN2‐F	CTATCATCTCTCAGTCAGGG
PAN2‐R	TTCACATGAAAGATATCGGC
PAN3‐F	TACAGACACCAAATCCTACTG
PAN3‐R	GTGAGAGAAAACTTGAGAGAAG
CNOT1‐F	CAGAGATTTTCCCCAAGAAC
CNOT1‐R	GATCCTGTCCATTAGAATGTC
CNOT2‐F	AGGAAAGTAGCTAAGGAGTTC
CNOT2‐F	TTTTTAGAAGGCTTGCTGAG
CNOT3‐F	GATGAGATCTTCAACCAGTC
CNOT3‐R	ATCATCTTCAGAGTTTTCCG
CNOT6‐F	TTGTCAGGTACTGCAAAAAG
CNOT6‐R	CTTGTCCTATCTGGTTCTTG
CNOT6L‐F	CTATTTGGAGCAGGTATGAAG
CNOT6L‐R	CATCAGAATACTCTGGGTCC
CNOT7‐F	CTCTAACTTGCCTGAAGAAG
CNOT7‐R	TCCTGTAATCCACCTTTGAG
CNOT8‐F	AAGTTGCTTACAGATTCTCG
CNOT8‐R	TCCCTTAAGATTTTTGCAGC
DCP1A‐F	AAAGAATGATTCCAGCTTCC
DCP1A‐R	TTATTCTGCTCCAGTCATAGG
DCP2‐F	GAAAGAATCAAAGTATAGGGG
DCP2‐R	GAAGCCCATTTGTTCTTTTC
EDC3‐F	CAGGTTGAATCCCAAAAATG
EDC3‐R	GCTCATTGGTGATAGATTCC
EDC4‐F	CAACCATAAGAAACAAGACCC
EDC4‐R	CACCACATCTTTAACTCTCG
DDX6‐F	GTACTACGCATATGTAACTGAG
DDX6‐R	GATGTTCCTGCCTCATTTTAG
LSM1‐F	CCCTCCAGCAAGTATCCATT
LSM1‐R	TCGAGGAATGGAAAGACCTC
EXOSC9‐F	ACACTGTATCACCTGAAGAG
EXOSC9‐R	GAAAAAGGCAAAACTGACAC
TTC37‐F	GTTARRGTGAGGACAATCTCTG
TTC37‐R	AAAGTACTAGATCCTGAAGAGG
WDR61‐F	CAAGAAGGAAAACTCTGAGAC
WDR61‐R	GTCCCAAAGACGAATATGAG
SKIV2L2‐F	ACACTACATTTTTCCAGCAG
SKIV2L2‐R	GTCCTTTTGTTCCTCCTTTC
IE1‐F	CAAGTGACCGAGGATTGCAA
IE1‐R	CACCATGTCCACTCGAACCTT
UL44‐F	TTTTCTCACCGAGGAACCTTTC
UL44‐R	CCGCTGTTCCCGACGTAAT
UL99‐F	GTGTCCCATTCCCGACTCG
UL99‐R	TTCACAACGTCCACCCACC
IL1B‐F	CTAAACAGATGAAGTGCTCC
IL1B‐R	GGTCATTCTCCTGGAAGG
CXCL3‐F	CCTCAAGAACATCCAAGTG
CXCL3‐R	CCCCTTGTTCAGTATCTTTTC
ANXA1‐F	GGAACTGAAGAGAGATCTGG
ANXA1‐R	TCTTCATTCACACCAAAGTC
LRRC15‐F	CGTTGCTGTTCCAAGCGTCCAT
LRRC15‐R	GCTCAGTGGTAGAAGAGACGGA
SPARC‐F	AGTGAATACATTAACGGTGC
SPARC‐R	AATGTGTGTTTAAGGCAGAG
NNMT‐F	GTTTGGTTCTAGGCACTCTGCAG
NNMT‐R	AGAGCCGATGTCAATCAGCAGG
GDF15‐F	CGAAGACTCCAGATTCCG
GDF15‐R	ACTTCTGGCGTGAGTATC
NOV‐F	GGAACCGTCAATGTGAGATGCTG
NOV‐F	GGCTTTGAGTGACTTCTTGGTGC
TNFRSF11‐F	GGTCTCCTGCTAACTCAGAAAGG
TNFRSF11‐R	CAGCAAACCTGAAGAATGCCTCC
COL15A1‐F	GGTGACACTGGTTTACCTGGCT
COL15A1‐R	GCCTTTCCAGAGGAATGTCCTC
HMGA2‐F	GAAGCCACTGGAGAAAAACGGC
HMGA2‐R	GGCAGACTCTTGTGAGGATGTC
PTX3‐F	CGAAATAGACAATGGACTCCATCC
PTX3‐R	CTCATCTGCGAGTTCTCCAGCA
SERPINB4‐F	CATGTTGATAGGTCAGGAAATG
SERPINB4‐R	ATTGATACGTCTTTTCTCCG
siRNAs:
control	Negative allstars cat #1027281	Qiagen
PARN #1	GAAAAGAAGGAGCGAUAUA	Dharmacon
PARN #2	CAUGAGAGGGCUUGCCGUA	Dharmacon
PAN2 #1	GACCUUGUUUGCUGGAUUA	Dharmacon
PAN2 #2	UCAAGGGUCUUUAUGAGAA	Dharmacon
PAN3 #1	AAAACAAGGUUGCGAGUAA	Dharmacon
PAN3 #2	CGACUUACUUCUAUACAGA	Dharmacon
CNOT1 #1	CUAUAAAGAGGGAACGAGA	Dharmacon
CNOT1 #2	GGCCAAAUUGUCUCGAAUA	Dharmacon
CNOT2 #1	CAUGAAUGGAGGAGACGUA	Dharmacon
CNOT2 #2	GGCAAGUUUAUACGGGCAA	Dharmacon
CNOT3 #1	GCACUAAGGCACAGUAUCU	Dharmacon
CNOT3 #2	AGACAUGGGUAGCGUCCAA	Dharmacon
CNOT6 #1	GAAAGAACGUGGCUAUAAU	Dharmacon
CNOT6 #2	GAGCACAGGUGGAGUAGAA	Dharmacon
CNOT6L #1	UGACAGCGCUGCACCUAAA	Dharmacon
CNOT6L #2	CCAAUUACACCUUUGAUUU	Dharmacon
CNOT7 #1	CAGCUAGGACUGACAUUUA	Dharmacon
CNOT7 #2	GGAGAAUUCAGGAGCAAUG	Dharmacon
CNOT8 #1	UUUCGUAGUUCCAUAGAUU	Dharmacon
CNOT8 #2	GAGAAUAGCCAGGUUAUCU	Dharmacon
DCP1A #1	Hs_DCP1A_6	Qiagen
DCP1A #2	Hs_DCP1A_7	Qiagen
DCP2 #1	GCUUGAAGGCACAACGUAA	Dharmacon
DCP2 #2	GUAUGGAGGUCUUGAGAAU	Dharmacon
EDC3 #1	CCUGAUAACAAACGCCUUA	Dharmacon
EDC3 #2	GGAGAUUGAUACCUAUGAA	Dharmacon
EDC4 #1	GGAUGGAGAUCGGCAUAAU	Dharmacon
EDC4 #2	GGACCAUGCCACCCAUUAA	Dharmacon
DDX6 #1	AGUAUGACCACCACUAUUA	Dharmacon
DDX6 #2	GAAGGACAAUAUACAAGCA	Dharmacon
LSM1 #1	CGAGATGGAAGGACACTTATA	Qiagen
LSM1 #2	CAGCCTCATCGAGGACATTGA	Qiagen
XRN1 #1	AGAUGAACUUACCGUAGAAUU	Burgess & Mohr (2015)
XRN1 #2	CAGGTCGTAAATATCAAATAA	Qiagen/Burgess & Mohr, (2015)
EXOSC9 #1	GCCAAGAAUGCUCCCAUAAU	van Dijk et al (2007)
EXOSC9 #2	GCAGAAAUUACAGAGCUAA[dT][dT]	Sigma
TTC37 #1	CAGUGAGACUCGACAGUAA	Dharmacon
TTC37 #2	GUGUUAUGGUCGUGCAUUA	Dharmacon
WDR61 #1	AGGAACUCAUGUCGGGAAA	Dharmacon
WDR61 #2	CAAAGAGAAUGUACGGAUU	Dharmacon
SKIV2L2 #1	GCACAUACCUCAGCGGGAA	Dharmacon
SKIV2L2 #2	AGGGAAAAGCAGCGUGUAA	Dharmacon
XRN2 #1	AAGAGUACAGAUGAUCAUGUU	West et al (2004)
XRN2 #2	ACACUGUAGUCAGUAUUAAUU	Wagschal et al (2012)
TNKS1BP1 #1	GAUUCACUGGGUACCUACA[dT][dT]	Sigma
TNKS1BP1 #2	CACUUUGUGCCUCCUGGGA[dT][dT]	Sigma
ANXA1	GUGUUCAAUACCAUCCUUA[dT][dT]	Sigma
LRRC15	CUGACUACCAUUCAGGUCA[dT][dT]	Sigma
SPARC	CUACAUCGGGCCUUGCAAA[dT][dT]	Sigma
Chemicals, enzymes and other reagents
Human IL‐4	R&D Systems	6507‐IL‐010/CF
Human IL‐12	R&D Systems	10018‐IL‐010
Human IFN‐beta	R&D Systems	8499‐IF‐010/CF
actinomycin D	Fisher	AAJ60148LB0
qScript XLT	Quanta	95132‐500
SsoAdvanced SYBR green supermix	Bio‐Rad	1725274
Software
SAMtools	Li et al (2009)
BEDtools	Quinlan (2014)
BBMAP	https://sourceforge.net/projects/bbmap/
TrimGalore	https://www.bioinformatics.babraham.ac.uk/projects/trim_galore/
Guppy v4.2.2
MiniMap2	Li (2018)
Nanopolish v0.13.3	https://github.com/jts/nanopolish
Other
NextSeq 550	Illumina
CellInsight CX7 LZR	Thermofisher
Dynabeads™ mRNA Purification Kit	Fisher	61006
NEBNext® Ultra™ II RNA Library Prep Kit for Illumina	NEB	E7300S
MinION MkIb	Oxford Nanopore Technologies Ltd