Table 1Experimentally confirmed examples of unproductive splicing

NameOrganismAS→PTCAS RegulatedPTC→Low AbundanceNMDNotesRefs.
a) Unproductive Splicing
FGFR2RatSide effect. Productive forms are tissue-specific.33, 67
Calpain-10Human16, 34, 35
TCR-betaHumanV(D)J cleanup. NMD strength boosted by sequence elements.68-70
ABCC4Human, Monkey, MouseHigh 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
HPRTHumanUnproductive transcripts are likely noise.71
b) Regulated Unproductive Splicing
MID-1Human, Mouse, Fugu38
FAHHumanPTC+ transcript is productive.27
U2AF35HumanMutually exclusive exons; PTC+ isoforms are an apparent side effect.73-77
MER2YeastSplicing 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, Mouse42, 43
ITSN-1Human, MouseProductive and unproductive isoforms are tissue-specific.80
b) Regulated Unproductive Splicing
LARDHumanPTC+ isoforms are abundant.81
ARD-1, NIPP-1HumanTranslation 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
d) Autoregulatory Unproductive Splicing Affecting Splicing Factors
CLKsHuman, Mouse, Ciona16, 53, 54, 82, 83
TIAR /TIA-1Human84
PTBHuman49, 51, 52
SRp20, SRp30bWorm85
AUF1Human86, 87
TRA2-betaHumanPTC+ 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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