Table 1.
Target constitutive factor | Location | Regulatory element | Trans-acting factor | Regulated exon | Gene | Mechanism of regulation | References |
---|---|---|---|---|---|---|---|
Silencers/repressors | |||||||
U2AF | Py | UCUU and UCUCU | PTB | 6B | β-tropomyosin | i | [25] |
UCUU | PTB | 3 | α-tropomyosin | i | [26–28] | ||
CUCUCU | PTB | N1 | c-Src | i | [16, 29, 30] | ||
UCUU | PTB | SM | α-actinin | i | [31, 32] | ||
CUCU like | PTB | 24 nt exon, EN and 5 | GABA receptor, Clathrin light chain B and NMDAR1 | i | [33] | ||
C/U-rich motifs | PTB | Groupb | Groupb | ia | [34] | ||
UUUUUGUUGUUUUUUUU | Sxl | 2 | Tra | i | [35, 36] | ||
8/10 U | ELAV | Terminal | Neuroglian | ia | [37] | ||
UG repeats | SUP-12 | 2A | ADF/Cofilin | ia | [38] | ||
UG | TDP43 | 9 | CFTR | ia | [39, 40] | ||
YGCU(U/G)Y | MBNL1 | 5 | cTNT | i | [41, 42] | ||
UCCCU | hnRNP K | 5a, 6 | Snap25, Runx1 | i | [43] | ||
UUUs | hnRNP C | 10 | CD55 | i | [44] | ||
Between Py and 3′ AG | CA repeats | hnRNP L | V10 | CD44 | ii | [45] | |
CaRRE | hnRNP L | STREX | Slo gene | ii | [46–48] | ||
CA repeats | hnRNPL | 20 | TJPI | ii | [49] | ||
GGGUGGGGG | hnRNP F/H | 3 | PRMT5 (group)b | ii | [50, 51] | ||
U2 | Near BP | UAGGG(A/U) | hnRNP A1 | 3 | Tat (HIV) | ii | [52] |
UGUGU and GU | CUGBP2 | N1 | NMDA R1 | ii | [53] | ||
UGU motifs | CUGBP2 | CUGBP2 | ii | [53] | |||
AUUAAC | QKI | 12 | NUMB | i | [54] | ||
ULM of SF1 | SPF45 | 6 | Fas | iia | [55] | ||
G rich | LS2 | Minigene | Ftc and PEP | iia | [56] | ||
U2AF of weaker 3′SSa | Upstream of 3′SS | UUUCUU, UUUUUC, UUUUCU | U2AF | Groupb | Groupb | iii | [22] |
ISS in IVS9 | SF2/ASF, SRp40 | 9 | CFTR | iii | [57] | ||
Constitutive factors e.g. U1, U2AF | Py | Stem loop | MBNL1 | 5 | cTNT | iv | [41, 42] |
U runs | Sxl | 3 | Sxl | iv | [58–60] | ||
CUCUCU | PTB | N1 | c-Src | iv | [16, 29, 30] | ||
UUUs | hnRNP C | 10 | CD55 (groupb) | iva | [61] | ||
Enhancers/activators | |||||||
U2AF, U2 snRNA | Py | CUG and UG motifs | CELF | SM, NM | Actinin | I | [62] |
U/G motifs | ETR-3 | 5 | cTNT | I | [63] | ||
U2AF interaction (Py) | DEK | Minigene | IgM-AdML | II | [64] | ||
Py | CAPER | 6 | VEGF | IIa | [65, 66] | ||
Py with 3′ CG or AG | hnRNP A1 | Groupb | Groupb | II | [67] | ||
CAUC | YB-1 | V5 | CD44 | II | [68] | ||
3′AG | 3′AG | Urp | Minigene | AdML | II | [69] | |
BP | AUUAAA | Sam68 | V5 | CD44 | II | [70] | |
Purine-rich ESE and BP | ASF/RS domain | Minigene | Actin, IgM | II | [71, 72] | ||
Between Py and 3′AG | UGC | nSR100 | Groupb | Groupb | II | [34] | |
U2AF of competing 3′SSa | Py | CU rich | PTB | Groupb | Groupb | III | [73] |
Constitutive factors e.g. U1, U2AF | Near 3′SS | Docking/selector | hrp36a | Minigene | Dscam | IV | [74–76] |
SR binding | U1, U2AF35 | Minigene | dsx | IV | [77–80] | ||
Artificial binding sites | hnRNP A/B or hnRNP F/H | Minigene | hnRNPA1 | IV | [81–84] |
For mechanisms of silencing/repression, i: competition, ii: steric hindrance, iii: competing 3′SS, or iv: local RNA secondary structure/looping out. For enhancement/activation, I: competition with a repressor for the same or overlapping RNA element, II: interaction with U2AF or U2 snRNA, III: competing 3′SS, or IV: local RNA secondary structure or longer range RNA loops
aPredicted
bGroup of regulated exons as detailed in the text