Table 1Experimentally confirmed examples of unproductive splicing

NameOrganismAS→PTCAS RegulatedPTC→Low AbundanceNMDNotesRefs.
a) Unproductive Splicing
FGFR2Rat••••Side effect. Productive forms are tissue-specific.33, 67
Calpain-10Human•••16, 34, 35
TCR-betaHuman•••V(D)J cleanup. NMD strength boosted by sequence elements.68-70
ABCC4Human, Monkey, Mouse•••High conservation of PTC-producing exons from mouse to human suggests that they are under ESE control, or that translation is reinitiated downstream of the PTC.59
HPRTHuman•••Unproductive transcripts are likely noise.71
b) Regulated Unproductive Splicing
MID-1Human, Mouse, Fugu••••38
POLBHuman••••71
FAHHuman••••PTC+ transcript is productive.27
NicastrinRat••••72
U2AF35Human••••Mutually exclusive exons; PTC+ isoforms are an apparent side effect.73-77
MER2Yeast••••Splicing is regulated by MER1, which is produced only in meiotic cells.45, 78
As a result, MER2 transcripts are productively spliced only during meiosis. In mitotic cells, a PTC+ form is produced and degraded.
ClC-1Human, Mouse••••42, 43
NDUFS4Human•••79
ITSN-1Human, Mouse•••Productive and unproductive isoforms are tissue-specific.80
b) Regulated Unproductive Splicing
LARDHuman••PTC+ isoforms are abundant.81
ARD-1, NIPP-1Human••Translation reinitiation. ARD1 is downregulated by NMD, but is nonetheless expressed. Also, ARD1 and NIPP1 may influence splicing via PP1.21
c) Autoregulatory Unproductive Splicing Not Affecting Splicing Factors
RPL30Yeast••••44
RPL12Worm••••46
AtGRP7Arabidopsis•••55
d) Autoregulatory Unproductive Splicing Affecting Splicing Factors
Sc35Human••••60
CLKsHuman, Mouse, Ciona••••16, 53, 54, 82, 83
TIAR /TIA-1Human••••84
PTBHuman••••49, 51, 52
SRp20, SRp30bWorm•••85
AUF1Human•••86, 87
TRA2-betaHuman••PTC+ forms are abundant, but are not translated, perhaps due to sequestration.88

Dots indicate direct experimental confirmation; lack of a dot means only that the experiment has not been performed to our knowledge. For instance, while it seems certain that ITSN-1 PTC+ isoforms are degraded by NMD, this has not been directly observed using Upf1 knockdown or another NMD assay. The few cases where an experiment was performed but yielded a negative result are noted. AS, alternative splicing.

From: Regulation of Gene Expression by Coupling of Alternative Splicing and NMD

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