Table 1.

Mammalian Polycistronic Genes

Gene	Protein(s)	Functional Category	Primary Protein Function	Secondary Protein Function	Disease Relevance	Mechanism of Expression of Second Cistron	Bicistronic Organization	Refs
TCP-Binding Protein	PRO1 (8.9kDa) / PRO2 (9.5kDa)	1	PRO1: Interacts with PRO2 to make a low-affinity phencyclidine binding entity that is part of a synaptic membrane complex	PRO2: Interacts with PRO1 to make a low-affinity phencyclidine binding entity that is part of a synaptic membrane complex	None reported	Putative IRES sequence between PRO1 ORF and PRO2 ORF	Tandem	[20]
FFAR1	GPR40 (31kDa) / GPR41 (38kDa)	2	GPR40: Long-chain fatty acid receptor	GPR41: Short-chain fatty acid receptor	None reported	IRES in the coding region of FFAR1 encodes GPR41	Tandem	[21–24]
meloe	MELOE-1 (4.3 kDa) / MELOE-2 (5.1 kDa)/ MELOE-3 (5.9 kDa)	2	MELOE-3: No known function; Poor immunogenicity, but is expressed in melanoma cells and normal melanocytes	MELOE-1: No known function; T cell antigen selectively expressed in melanoma cells MELOE-2: No known function; T cell antigen selectively expressed in melanoma cells	Potential target for T cell immune therapy for melanoma	IRES upstream of the ORFs of MELOE-1 and MELOE-2; MELOE-3 is produced by cap- dependent translation	Tandem	[15, 16, 25]
MTPN	Myotrophin (12.9 kDa) / MPD6 (6.4 kDa)	3	Myotrophin: Allows dimerization of NFκB in cardiac tissue	MPD6: No known function; antigen upregulated in response to interferon-α (IFN-α)	Myotrophin induces cardiac hypertrophy; MPD6 elicits humoral immune response in some cancers	MPD6 antigen ORF is located in the 3' UTR region of the myotrophin gene and is translated by an IRES located upstream	Tandem	[30]
Connexin 43	Cx43 (43kDa) / Cx43-CT (20kDa)	3	Cx43: Highly abundant connexin with junctional and non-junctional function	Cx43-CT: Implicated in autoregulating the trafficking of Cx43	Hypoplastic left heart syndrome 1, Oculodentodigital dysplasia, Syndactyly type III Craniometaphyseal dysplasia	Putative IRES or Cap-dependent internal translation	Overlapping	[45, 46]
Connexin 55.5	Cx55.5 (56kDa) / CT-11 (16kDa)	3	Cx55.5: A connexin exclusively expressed in horizontal cells	CT-11: Has nuclear translocation and may be involve in regulating light- dependent plasticity	Mutations in human homolog associated with cataracts	Putative IRES upstream of ATG at nucleotide position 1201	Overlapping	[47]
pVHL-19	pVHL-30 (30kDa) / pVHL-19 (19kDa)	3	pVHL-30: Tumor suppressor residing in cytosol	pVHL-19: Comparable tumor suppressor in nucleus and cytoplasm with possibly different molecular substrates	von Hippel-Lindau disease	Mechanism not investigated	Overlapping	[48, 49]
CdcL1/CdcL2 (PITSLRE genes)	p110 (PITSLRE) (110 kDa) / p58(PITSLRE) (58kDa) cyclin- dependent kinase isoforms	3	p110 (PITSLRE): Regulates transcriptional processing by binding elongation factors and RNA-binding proteins	p58 (PITSLRE): Binds cyclin D3 in G2/M phases of the cell cycle	None reported	Increased translation of p58 during G2/M phase due to Unr and phosphorylated eIF-2α binding via IRES near C-terminal end of p110	Overlapping	[26]
SNRPN/SNURF	SmN (24.6kDa) / SNURF (8.4kDa)	3	SmN: Splicing factor important for RNA processing	SNURF: Potentially implicated in the regulatory mechanism behind gene imprinting	Prader-Willi syndrome; Angelman syndrome	Mechanism not investigated	Tandem	[50]
GDF1-LASS1	GDF1 (39kDa) / LASS1 (39kDa)	3	GDF1: TGFβ superfamily member implicated in cell growth and differentiation with role in left-right patterning and mesoderm induction	LASS1 (CerS1) ceramide synthase: TGFβ superfamily member implicated in cell growth and differentiation; catalyzes the synthesis of C18 ceramide in a fumonisin B1- independent manner	GDF1: cardiovascular malformations; LASS1: progressive myoclonic epilepsy-8 (EPM8)	Mechanism not Investigated	Tandem	[51]
CACNA1A	a1A (220kDa) / a1ACT (75kDa)	3	a1A: Voltage-gated calcium channel subunit involved in pre and postsynaptic Ca2+ signaling, gene expression	a1ACT: Transcription factor important for expression of neural and Purkinje cell development genes	Spinocerebellar ataxia type 6 (SCA6), Episodic ataxia type 2 (EA-2), Familial hemiplagic migraine type 1 (FHM-1), Epilepsy	a1ACT is made via an IRES in the C-terminal coding region of CACNA1A	Overlapping	[27–29]
Notch2	Notch2 (265kDa) / N2ICD (v-Notch2) (70kDa)	4	Notch2: Cell surface transmembrane receptor involved in cell fate decision during development by release of N2ICD	N2ICD: The intracellular domain decoupled and independent of Notch2 surface ligand	Hajdu-Cheney Syndrome; Alagille syndrome	Proposed dual mechanism of second cistron initiation: ribosomal reinitiation and IRES both equally contributing to expression of N2ICD	Overlapping	[31–37]
Her2	HER2 (185 kDa) / HER2 CTF (70 kDa)	4	HER2: Tyrosine kinase receptor canonically known to act in secretory and endocytic pathways but also acts within the cell nucleoplasm and nucleus	HER2 CTFs: C-terminal fragments that encompass the transmembrane and cytoplasmic domains of full length HER2, are associated with nodal metastasis, and localize to the cytoplasm and nucleus of cells	Hereditary breast cancer, cancer metastasis, tumor development	Hypothesized IRES within coding region (not confirmed); two methionines at positions 611 and 687 act as initiators of translation for CTFS	Overlapping	[38]