RBM5 (RNA binding motif protein 5)

2007-02-01   Mirna Mourtada-Maarabouni 

School of Life Sciences, Keele University, Keele, Staffs, ST5 5BG, United Kingdom




Atlas Image
RBM5/LUCA-15 splice variants. Boxes represent the exons, intronic sequences are represented by horizontal lines. The arrows point to the STOP codon in the protein coding sequence.


The gene spans about 30.03 Kb. Orientation plus strand. At least 25 exons.


Full length RBM5 has 3.1 Kb, 2448 bp open reading frame. The gene encodes a number of alternative splice variants, identified by reverse transcription polymerase chain reaction. One splice variant lacks exon 6, RBM5delta6. Three other RNA splice variants retain intronic sequences, RBM5+5+6 retains introns 5 and 6, RBM5+6 retains intron 6 and clone 26 which is a partial cDNA containing an open reading frame and terminates within intron 6. A 326 bp antisense cDNA that maps to the intronic region of RBM5, je2, has also been identified. Both, RBM5delta6 and clone 26 cDNAs have been cloned.



Full length RBM5 encodes a protein with a molecular mass of about 90 kDa (815 amino acids). The protein has two RNA Binding Domains (RBD), also recognized as RNA Recognition Motif (RRM). RBM5 structure also features other functional motifs, which includes two putative zinc-finger DNA binding motifs, two bipartite nuclear localisation signals and a G-patch domain (a conserved domain in eukaryotic RNA-processing proteins and type D retroviral polyproteins), suggesting a role for RBM5/LUCA-15 in RNA processing. In addition, the C-terminal region of RBM5/LUCA-15 contains several domains including a glutamine rich domain (362-385), which is thought to serve as protein-protein interaction site in certain RNA- and DNA- binding proteins.
RBM5delta6 encodes a protein of 17 kDa, due to a frameshift mutation caused by the deletion of exon 6. The only functional motif retained by this truncated protein is the arginine/glycine-rich amino terminal region. A putative 21 kDa is reported to be encoded by RBM5+5+6 and clone 26, as revealed by an in vitro transcription/translation study in rabbit reticulocyte lysate.


Full length RBM5 and its alternative splice variants RNA are widely expressed in both primary tissue and cell lines. Northern blot analysis revealed higher expression in skeletal and heart muscles and pancreas. The expression of the full length RBM5 mRNA is reported to be high in adult thymus and low in the foetal thymus, suggesting that its expression is developmentally regulated. Full length RBM5/LUCA-15 is reported to be down-regulated in breast cancer specimens, in 82% of primary non-small-cell lung carcinoma specimens and in many lung cancer cell lines and in vestibular schwannomas (27 fold reduction). The expression of RBM5delta6 RNA is highest in transformed cells. The full length RBM5 protein is ubiquitously expressed in human tissues. It was found to be downregulated in 73% of primary non-small-cell lung carcinoma specimens compared to normal adjacent tissue. RBM5/LUCA-15 was one of the antigens identified by autologous antibody in patients with renal carcinoma. Overexpression of je2, the 326 bp antisense sequence, resulted in the downregulation of the RBM5 protein (95 kDa) and the upregulation of the 17 kDa protein (RBM5delta6).


RBM5 protein includes bipartite nuclear localisation signals suggesting its localisation to the nucleus.


RBM5/LUCA-15 is among the 35 genes located within the 370 kb overlapping lung cancer homozygous deletion region at 3p21.3. RBM5 has been implicated in the control of cell death by apoptosis and cell proliferation. RBM5s involvement in apoptosis and malignancy has been the focus of many recent studies, with all results converging on a role for RBM5/LUCA-15 as a Tumor Suppressor Gene (TSG). RBM5 splice variants have been shown to function as regulators of apoptosis. Stable expression of Je2, in human T-cell lines CEM-C7 and Jurkat produced marked inhibition of Fas-mediated apoptosis and conferred protection from apoptosis induced by other stimuli. RBM5delta6 inhibits CD95-mediated apoptosis as well as accelerating cell proliferation.
Overexpression of the full length RBM5 in CEM-C7 and Jurkat T-cell lines suppressed cell proliferation both by inducing apoptosis and by inducing cell cycle arrest in G1. Consistently, RBM5/LUCA-15 overexpression also inhibited human lung cancer cell growth (A549 non-small cell lung cancer line) by increasing apoptosis and inducing cell cycle arrest in G1. This inhibition of cell growth was reported to be associated with decreased cyclin A and phosphorylated RB and an increase in the level of the proapototic protein Bax. Introducing RBM5/LUCA-15 into breast cancer cells that had 3p21-22 deletions reduced both anchorage-dependent and anchorage-independent growth. RBM5/LUCA-15 also is reported to suppress anchorage-dependent and anchorage-independent growth in A9 mouse fibrosarcoma cells and to inhibit their tumour forming activity in nude mice. RBM5/LUCA-15 was one of the nine genes down-regulated in metastasis and it has been included in the 17 common gene signature associated with metastasis identified in multiple solid tumour types. Solid tumours carrying this gene expression signature had high rates of metastasis and poor clinical outcome. Microarray-based analysis of changes in gene expression caused by the modulation of the level of RBM5/LUCA-15 were carried out. Among 5603 genes on cDNA microarray, 35 genes, well known for their roles in the cell cycle as well as in apoptosis, were found to be differentially expressed as a result of RBM5/LUCA-15 overexpression in CEM-C7 cells.
These RBM5/LUCA-15 modulated genes include a number of cyclin-dependent kinase complexes, most notably CDK2 and three putative oncogenes which are down-regulated by RBM5/LUCA-15. These are Pim-1, a serine/threonine kinase, ITPA (inosine triphosphate pyrophosphatase) and Amplified in Breast cancer 1 (AIB1). Other functionally important genes modulated by RBM5/LUCA-15 are well established to play specific anti apoptotic roles such as BIRC4 (AIP3), BIRC3 (cIAP2, MIHC), Mcl-1, a member of the Bcl-2 family of apoptosis suppressors, and TRAF1, supporting a role for RBM5/LUCA-15 in apoptosis. Other genes upregulated by RBM5/LUCA-15 include Stat5b, Annexin I and Bone Morphogenetic Protein 5 (BMP5), implicated in apoptosis, immunosuppression and organ development respectively.


RBM5 shares 30% amino acid sequence homology with its immediate telomeric neighbor, the putative tumor suppressor gene RBM6. Another RNA Binding Motif protein that shares high homology with RBM5 (53% at the amino acid level) is RBM10. The RBM10 gene is located on the X chromosome at p11.23. No function has yet been determined for RBM10. The mouse RBM5 gene is 90% identical on cDNA level and 97% on protein level. The fly proteome contain three similar proteins, of which CG4887 gene product shows 43% similarity. The rat binding protein S1-1 has similar domain structure and is close in amino acid sequence to RBM5.



Mutations in the RMB5 gene have not been found in lung cancer. RBM5 is reported to be downregulated in RAS-transformed Rat-1 cells, in samples from breast cancer, in human schwannomas and in about 75% of primary lung cancers specimens. RBM5 was one of the nine genes down-regulated in metastasis in primary tumors and it has been included in the 17 common gene signature associated with metastasis identified in multiple solid tumour types. Solid tumours carrying this gene expression signature had high rates of metastasis and poor clinical outcomes.

Implicated in

Entity name
Lung cancer and many other cancers
RBM5 is located at the human chromosomal locus 3p21.3, which is strongly associated with lung cancer and many other cancers, including head and neck, renal, breast and female genital tract. More than 90% of freshly microdissected primary lung cancers display loss of heterozygosity (LOH) of 3p21.3. RBM5 is implicated in apoptosis and in cell cycle regulation.
The ability of RBM5/LUCA-15 to inhibit the growth of transformed cells fulfils one of the criteria for a tumor suppressor. The simultaneous changes in proliferation and inhibition of apoptosis brought about by dysregulation of the RBM5/LUCA-15 locus are likely to be of major significance in oncogenesis.


Pubmed IDLast YearTitleAuthors
104700321999G-patch: a new conserved domain in eukaryotic RNA-processing proteins and type D retroviral polyproteins.Aravind L et al
80365111994Conserved structures and diversity of functions of RNA-binding proteins.Burd CG et al
102135081999Molecular cloning of a candidate tumor suppressor gene, DLC1, from chromosome 3p21.3.Daigo Y et al
83900351993A homozygous deletion on chromosome 3 in a small cell lung cancer cell line correlates with a region of tumor suppressor activity.Daly MC et al
103536021999DEF-3(g16/NY-LU-12), an RNA binding protein from the 3p21.3 homozygous deletion region in SCLC.Drabkin HA et al
110296602000LUCA15, a putative tumour suppressor gene encoding an RNA-binding nuclear protein, is down-regulated in ras-transformed Rat-1 cells.Edamatsu H et al
95004671998Human lung cancer antigens recognized by autologous antibodies: definition of a novel cDNA derived from the tumor suppressor gene locus on chromosome 3p21.3.Güre AO et al
93658291997Differential elimination of 3p and retention of 3q segments in human/mouse microcell hybrids during tumor growth.Imreh S et al
76214111995A group of NotI jumping and linking clones cover 2.5 Mb in the 3p21-p22 region suspected to contain a tumor suppressor gene.Kashuba VI et al
91118631997Deletions of the short arm of chromosome 3 in solid tumors and the search for suppressor genes.Kok K et al
110855362000The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium.Lerman MI et al
171958682006The antiapoptotic RBM5/LUCA-15/H37 gene and its role in apoptosis and human cancer: research update.Maarabouni MM et al
165461662006Candidate tumor suppressor LUCA-15/RBM5/H37 modulates expression of apoptosis and cell cycle genes.Mourtada-Maarabouni M et al
1658516320063p21.3 tumor suppressor gene H37/Luca15/RBM5 inhibits growth of human lung cancer cells through cell cycle arrest and apoptosis.Oh JJ et al
120369352002A candidate tumor suppressor gene, H37, from the human lung cancer tumor suppressor locus 3p21.3.Oh JJ et al
124691222003A molecular signature of metastasis in primary solid tumors.Ramaswamy S et al
105084791999Antigens recognized by autologous antibody in patients with renal-cell carcinoma.Scanlan MJ et al
155149232005RNA binding motif (RBM) proteins: a novel family of apoptosis modulators?Sutherland LC et al
103529381999A comparison of genomic structures and expression patterns of two closely related flanking genes in a critical lung cancer region at 3p21.3.Timmer T et al
86033901996Construction of a 600-kilobase cosmid clone contig and generation of a transcriptional map surrounding the lung cancer tumor suppressor gene (TSG) locus on human chromosome 3p21.3: progress toward the isolation of a lung cancer TSG.Wei MH et al
122186282002cDNA microarray analysis of vestibular schwannomas.Welling DB et al

Other Information

Locus ID:

NCBI: 10181
MIM: 606884
HGNC: 9902
Ensembl: ENSG00000003756


dbSNP: 10181
ClinVar: 10181
TCGA: ENSG00000003756


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Gene ExpressionREACTOMER-HSA-74160
Processing of Capped Intron-Containing Pre-mRNAREACTOMER-HSA-72203
mRNA SplicingREACTOMER-HSA-72172
mRNA Splicing - Major PathwayREACTOMER-HSA-72163

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
243321782013RBM5, 6, and 10 differentially regulate NUMB alternative splicing to control cancer cell proliferation.98
188518352008RBM5/Luca-15/H37 regulates Fas alternative splice site pairing after exon definition.75
188406862008Up-regulation of the proapoptotic caspase 2 splicing isoform by a candidate tumor suppressor, RBM5.46
1658516320063p21.3 tumor suppressor gene H37/Luca15/RBM5 inhibits growth of human lung cancer cells through cell cycle arrest and apoptosis.34
225692502012Tumor suppressor RBM5 directly interacts with the DExD/H-box protein DHX15 and stimulates its helicase activity.24
151923302004LUCA-15/RBM5, a putative tumour suppressor, enhances multiple receptor-initiated death signals.20
275204492016RBM5-AS1 Is Critical for Self-Renewal of Colon Cancer Stem-like Cells.17
203099332011p53 transactivation is involved in the antiproliferative activity of the putative tumor suppressor RBM5.14
203386642010RBM5/H37 tumor suppressor, located at the lung cancer hot spot 3p21.3, alters expression of genes involved in metastasis.14
195597722009Identification and characterisation of a novel antisense non-coding RNA from the RBM5 gene locus.13


Mirna Mourtada-Maarabouni

RBM5 (RNA binding motif protein 5)

Atlas Genet Cytogenet Oncol Haematol. 2007-02-01

Online version: http://atlasgeneticsoncology.org/gene/42069/rbm5-(rna-binding-motif-protein-5)