Table 1 Trans-acting factors involved in Bcl-x splicing regulation

RNA binding proteins

Sam68

Recruit hnRNP A1 to certain regions.

Bcl-xS

[26]

SRSF1 (ASF/SF2)

Compete with hnRNP A1.

Bcl-xL

[26, 35]

SRSF10

Collaborate with hnRNP A1/A2 and Sam68.

Bcl-xS

[29]

SRSF2 (SC35)

As a direct transcriptional target of E2F1.

Bcl-xS

[30]

SRSF3

Favor the selection of the 5' DSS.

Bcl-xS

[28]

SRSF7

Favor the selection of the 5' DSS.

Bcl-xL

[28]

SRSF9 (SRp30c)

Bind to ML2 and AM2.

Bcl-xL

[21]

TRA2β

Favored selection of the 5' DSS.

Bcl-xS

[28]

hnRNP F/H

Bind to B2G region.

Bcl-xS

[22, 36]

PTBP1 (hnRNP I)

Bind to polypyrimidine to promote 5' DSS selection

Bcl-xS

[28]

hnRNP A1

Interact with Sam68.

Bcl-xS

[25, 26]

hnRNP A2/B1

Regulated by Fyn activity.

Bcl-xL

[37]

hnRNP K

Bind to silencer element of the 5' DSS.

Bcl-xL

[20]

RBM4

Antagonize oncogenic SRSF1.

Bcl-xS

[38]

RBM10 (S1-1)

Block the GGGUAAG of exon 2.

Bcl-xS

[39]

RBM11

Antagonize SRSF1.

Bcl-xS

[40]

RBM25

Bind to CGGGCA sequence within exon 2.

Bcl-xS

[41]

Transcription factors

E2F1

Upregulate SC35 protein expression.

Bcl-xS

[30]

FBI-1

Interact with Sam68 and affects its binding.

Bcl-xL

[31]

TCERG1

Increase the elongation rate of RNAPII.

Bcl-xS

[32]

FOXP3

Repress hnRNPF binding to 5'DSS.

Bcl-xL

[33]

SAP155 (SF3B1)

Bind to CRCE 1 region.

Bcl-xL

[42]

Signal pathway

PKC signal

Through SB1 to repress the 5'DSS splicing.

Bcl-xL

[43]

PI3K/PKC_ι signal

Regulate SAP155-CRCE1 complex formation.

Bcl-xL

[44]

LPS/PRMT2 or TNF-α pathway

Interact with Sam68 and regulate its subcellular localization via its SH3 domain.

Bcl-xL

[45]

G4s and G4s ligands

G-quadruplexes (G4s)

Close to the two alternative 5'SS to compete with other RNA structures or proteins

Bcl-xS or Bcl-xL

[46, 47]

G-quadruplex ligands (GQC05)

Stabilize G-quadruplexes.

Bcl-xS

[46]

EJC

Exon junction complex ( EJC )

RNPS1 and core EJC proteins control Bcl-x splicing through cis-acting elements SB1.

Bcl-xL

[48]