rev. 12/09/19
RNA Lifecycle Diagram
3
’
5’
Decay
I
I
I
— Digested RNA— hrRNP— Exon —Reader
—Adenosine
—Inosine
—
—Uridine
—Pseudouridine
Key
5
’
3
’
Decay
Nascent pre-mRNP
DNA
RNA
DNA
mRNA
5
’
mRNA Capping
5
’
RNA
RNA
Intron
Exon
Exon
Exon
Exon
G
m
7
G
m
7
G
m
7
G
m
7
G Cap
mRNA
A-to-I Editing
Deadenylation
Decapping
RNA
RNA
Intron
m
7
G Cap
A
A
A
Exon
Exon
Nascent Pre-mRNP
DNA
Modifications
Translation Initiation
Splicing
3
’
End Processing
m6A Writers, Erasers, Readers
Pseudouridylation
Spliceosome
Polyadenylation Complex
Intron
Exon
Exon
m
7
G Cap
A
mRNA
EJC:CASC3RBM8A MAGOH PYM1
Endonuclease (e.g. IRE1, PMR1, RNAse, MRP)
u
ψ
Intron
5
’
3
’
m
7
G Cap
Â-30 -73 -100 -160
Â-50 -64/tau -77
m
7
G Cap
Poly A Site
Nascent Pre-mRNP
DNA
Nascent Pre-mRNP
DNA
AAAAAAA
5
’
m
7
G Cap
AUG
m
7
G Cap
Other RBPs: ÂPHAX NXF1 NXT1
ÂFYTTD1 XP01
Nucleus
Cytoplasm
m
7
G Cap
EJC:CASC3RBM8A MAGOH PYM1
Translation • Elongation FactorsSilencing • •
Destabilization/Decay • Nonsense-Mediated Decay • Non-Stop Decay • No-Go Decay • ARE-Mediated Decay
Deadenylation-Dependent mRNA Decay
Endonuclease-Mediated mRNA Decay
Deadenylation-Independent mRNA Decay
ORF
5
’
UTR
3
’
UTR
m
7
G
AAAA
AAAA
m
7
G
AA
m
7
G
5
’
3
’
Decay
5
’
3
’
Decay
3
’
5
’
Decay
m
7
G
Scavenger Decapping
m
7
G
m
7
G
m
7
G
AAAA
m
7
G
AAAA
AAAA
m
7
G
Transcription
CF1
PAP
POL
CTD
POLII/ POLR2
WTAP
PRC2
FTO
YTH
ALKBH5
RBM15
VIRMA
RNMT
RNGTT
METTL14
METTL3
TREX
TREX
ADAR
NCB
ADAR
CPSF
CPSF
ADAR
U2/sf
U1
SR
U1
U4/u5/u6
LIN28A/B
DKC1
PUS1/3
DDX3X
DDX5
SR
SR
SR
SR
TREX
CPSF
SR
SR
SR
NCB
EJC
POLII/ POLR2
CPSF
POLII/ POLR2
CPSF
POLII/ POLR2
CSTF
PABP
CPSF
PABP
CFII
TREX
eIF3
HNRNP
LSM1-7
ELAVL
4OS
PABP
SR
SR
SR
eIF4A
eIF4G
NCB
PABP
CPSF
4E-BP
eIF4E
CCR4-NOT or PARN
LSM1-7
DCP1
DCP2
LSM1-7
XRN1
DCP5
DCP1
EDC3
RPS28B
DCP2
XM1
XRN1
EDC3
RPS28B
NCB
NCB
NCB
Exosome
Exosome
RNA Polymerase II
CPSF
hrRNP
hrRNP
hrRNP
EIF4A3
EIF4A3
eIF4E
CSTF
Dicer
RISC/Ago2
m6A
N6-methyladenosine
CF1
PAP
POL
CTD
POLII/ POLR2
WTAP
PRC2
FTO
YTH
ALKBH5
RBM15
VIRMA
RNMT
RNGTT
METTL14
METTL3
TREX
TREX
ADAR
NCB
ADAR
CPSF
CPSF
ADAR
U2/sf
U1
SR
U1
U4/u5/u6
LIN28A/B
DKC1
PUS1/3
DDX3X
DDX5
SR
SR
SR
SR
TREX
CPSF
SR
SR
SR
NCB
EJC
POLII/ POLR2
CPSF
POLII/ POLR2
CPSF
POLII/ POLR2
CSTF
PABP
CPSF
PABP
CFII
TREX
eIF3
HNRNP
LSM1-7
ELAVL
4OS
PABP
SR
SR
SR
eIF4A
eIF4G
NCB
PABP
CPSF
4E-BP
eIF4E
CCR4-NOT or PARN
LSM1-7
DCP1
DCP2
LSM1-7
XRN1
DCP5
DCP1
EDC3
RPS28B
DCP2
XM1
XRN1
EDC3
RPS28B
NCB
NCB
NCB
Exosome
Exosome
RNA Polymerase II
hrRNP
hrRNP
hrRNP
EIF4A3
EIF4A3
eIF4E
Dicer
RISC/Ago2
m6A
N6-methyladenosine
CPSF
CSTF