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RPL26 (ribosomal protein L26)

Written2010-09Kristy Boggs, Michael Kastan
Department of Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)L26
Other alias
HGNC (Hugo) RPL26
LocusID (NCBI) 6154
Atlas_Id 47470
Location 17p13.1  [Link to chromosome band 17p13]
Location_base_pair Starts at 8280834 and ends at 8286565 bp from pter ( according to hg19-Feb_2009)  [Mapping RPL26.png]
 
Fusion genes
(updated 2016)
HOXB9 (17q21.32) / RPL26 (17p13.1)RPL26 (17p13.1) / ESF1 (20p12.1)

DNA/RNA

Note Human RPL26 cDNA was derived from mRNA isolated from human non-small cell lung cancer cell line SW-1573.
 
  RPL26 gene. Exons are represented by boxes (red corresponds to the 5' and 3'UTR; blue corresponds to the protein encoding sequence). The size of each exon is shown above the exon and the position of the exon within the gene is shown below each exon.
Description RPL26 gene is 5731 bp in length consisting of 4 exons (the first is non-coding) and 3 introns located on the minus strand of chromosome 17p. Exon 2 contains the translation initiator ATG and exon 4 contains the stop codon. The promoter of the RPL26 gene contains an oligopyrimidine tract, TATA-like sequence and a possible binding site for Ets protein family members. Transcription starts at a C-residue within the oligopyrimidine tract.
Transcription RPL26 mRNA transcript is 602 bp in length.
It has been reported that ribosomal protein L26 mRNA is preferentially expressed in normal early placenta (NEP) compared to L26 mRNA levels in gestational trophoblastic diseases (GTDs).
Pseudogene 36 human pseudogenes (Entrez Gene).
An RPL26 processed pseudogene has been found within the intron of a functional RPS2 gene.

Protein

 
  RPL26 protein. KOW: conserved RNA binding motif.
Description Eukaryotic ribosomes consist of a small 40S and large 60S subunit. These ribosomal subunits are composed of 4 ribosomal RNAs and over 80 ribosomal proteins. RPL26 is a ribosomal protein associated with the large 60S subunit of the ribosome and contains a KOW motif, a conserved RNA-binding motif present in many ribosomal proteins.
Expression Widely expressed.
Localisation RPL26 protein is primarily localized in the cytoplasm, to a lesser extent, it is found in the nucleoplasm and nucleolus.
Function Ribosome biogenesis/stability: ribosome biogenesis is associated with proliferation, cell growth and stress responses. Eukaryotic ribosomes consist of a 40S and 60S subunit that are composed of 4 ribosomal RNAs (rRNAs) and approximately 80 ribosomal proteins, ribosomal protein L26 is associated with the 60S subunit of the ribosome. The ratio of rRNAs to ribosomal proteins is tightly regulated within the cell. An excess or reduction in either component can disrupt ribosome assembly. In a recent study investigating the role of ribosomal proteins in mammalian biogenesis, several ribosomal proteins, including RPL26, were individually depleted in HeLa cells using siRNAs. RPL26 knockdown resulted in a decrease in the amount of 60S ribosomal subunit as well as fully assembled ribosomes and polysomes. Also, knockdown of RPL26 resulted in a significant decrease in synthesis of 28S rRNA (associated with 60S subunit) and interestingly 18S rRNA (associated with 40S subunit). This work underscores the importance of RPL26, amongst other ribosomal proteins, in ribosome biogenesis.

Translational regulation of mRNA: protein stability has largely been attributed to increases in p53 protein levels following DNA damage however, more recent reports show an increase in translation of p53 mRNA also contributes to p53 protein levels and is necessary for optimal induction of p53 following irradiation. In particular, the RPL26 protein binds to the 5'UTR of p53 mRNA following irradiation enhancing the association of p53 mRNA with polysomes thereby increasing translation of p53 mRNA. Furthermore, RPL26-mediated enhancement of p53 translation not only resulted in an increase in p53 protein levels but also in the transactivation of downstream p53 targets as demonstrated by the induction of G1 cell-cycle arrest and enhanced apoptosis.
More recently, it has been shown that RPL26 binding to p53 mRNA following DNA damage requires not only the 5'UTR of p53 mRNA but also the 3'UTR. The interaction between complimentary sequences found within the 5' and 3'UTR of p53 mRNA creates a double-stranded RNA structure necessary for RPL26 binding to p53 mRNA. Disruption of this double-stranded RNA structure, either by base mutations in the two complementary UTR sequences or with a single-stranded oligonucleotide targeting the 5'-3'UTR base pairing, abolishes binding of RPL26 to the p53 mRNA, RPL26-enhancement of p53 translation and p53-mediated apoptosis.
Ribosomal proteins are an integral component of protein synthesis however, evidence is emerging that ribosomal proteins have additional functions outside of protein synthesis. Translational regulation of RPL26 mRNA has been shown to be an important feature of LPS-activation of human dendritic cells (DCs). During the early phase of DC maturation via LPS-activation, RPL26 mRNA is translated while during late phase of DC maturation, RPL26 mRNA is translationally down-regulated as demonstrated by a reduction in polysomal-bound RPL26 mRNA and overall RPL26 protein levels. Transcription of the RPL26 gene remained unchanged in all phases of LPS-activated DC maturation.

Interaction with MDM2: regulation of p53 protein levels within the cell has largely been attributed to changes in p53 half-life. In the absence of DNA damage, p53 protein levels are kept low via p53 interaction with MDM2, an E3-ubiquitin ligase that targets p53 for proteasomal degradation. After DNA damage, MDM2-mediated proteasomal degradation of p53 is abrogated allowing p53 protein levels to rapidly accumulate. Recently is has been reported that MDM2 can also regulate p53 protein levels by targeting RPL26-mediated translation of p53 mRNA. In the absence of DNA damage, MDM2 binds to and polyubiquitinates RPL26 targeting the RPL26 protein for proteasomal degradation thereby attenuating RPL26-enhancement of p53 translation. Following DNA damage by irradiation, the inhibitory effect of MDM2 on RPL26-enhancement of p53 translation is abrogated resulting in RPL26-mediated translation of p53 mRNA and accumulation of p53 protein.
In addition to translational regulation of p53 mRNA, it has also been reported that overexpressed RPL26 can regulate p53 protein stability through interaction with MDM2. The interaction of RPL26 with MDM2 stabilizes total p53 protein levels by blocking MDM2-mediated ubiquitination of p53 protein and its subsequent proteasomal degradation.

Homology RPL26, a member of the L24P family of ribosomal proteins, is an evolutionary conserved protein found in all eukaryotes including M. musculus, R. norvegicus, D. melanogaster, C. elegans, S. pombe, S. cerevisiae.
HomoloGene: 113207. Gene conserved in Eukaryota (HomoloGene).

Mutations

Note No human RPL26 mutations have been reported. A cell line derived from a UV-induced murine tumor with both alleles of the RPL26 gene harboring different point mutations (P22S and H96Y) has been reported.

Bibliography

Point mutation in essential genes with loss or mutation of the second allele: relevance to the retention of tumor-specific antigens.
Beck-Engeser GB, Monach PA, Mumberg D, Yang F, Wanderling S, Schreiber K, Espinosa R 3rd, Le Beau MM, Meredith SC, Schreiber H.
J Exp Med. 2001 Aug 6;194(3):285-300.
PMID 11489948
 
Ribosomal protein mRNAs are translationally-regulated during human dendritic cells activation by LPS.
Ceppi M, Clavarino G, Gatti E, Schmidt EK, de Gassart A, Blankenship D, Ogola G, Banchereau J, Chaussabel D, Pierre P.
Immunome Res. 2009 Nov 27;5:5.
PMID 19943945
 
5'-3'-UTR interactions regulate p53 mRNA translation and provide a target for modulating p53 induction after DNA damage.
Chen J, Kastan MB.
Genes Dev. 2010 Oct 1;24(19):2146-56. Epub 2010 Sep 13.
PMID 20837656
 
Identification of multiple differentially expressed messenger RNAs in normal and pathological trophoblast.
Durand S, Abadie P, Angeletti S, Genti-Raimondi S.
Placenta. 2003 Feb-Mar;24(2-3):209-18.
PMID 12566248
 
Genetic transfer of non-P-glycoprotein-mediated multidrug resistance (MDR) in somatic cell fusion: dissection of a compound MDR phenotype.
Eijdems EW, Borst P, Jongsma AP, de Jong S, de Vries EG, van Groenigen M, Versantvoort CH, Nieuwint AW, Baas F.
Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3498-502.
PMID 1348862
 
Mdm2 regulates p53 mRNA translation through inhibitory interactions with ribosomal protein L26.
Ofir-Rosenfeld Y, Boggs K, Michael D, Kastan MB, Oren M.
Mol Cell. 2008 Oct 24;32(2):180-9.
PMID 18951086
 
The role of human ribosomal proteins in the maturation of rRNA and ribosome production.
Robledo S, Idol RA, Crimmins DL, Ladenson JH, Mason PJ, Bessler M.
RNA. 2008 Sep;14(9):1918-29. Epub 2008 Aug 12.
PMID 18697920
 
Regulation of p53 translation and induction after DNA damage by ribosomal protein L26 and nucleolin.
Takagi M, Absalon MJ, McLure KG, Kastan MB.
Cell. 2005 Oct 7;123(1):49-63.
PMID 16213212
 
The human ribosomal protein genes: sequencing and comparative analysis of 73 genes.
Yoshihama M, Uechi T, Asakawa S, Kawasaki K, Kato S, Higa S, Maeda N, Minoshima S, Tanaka T, Shimizu N, Kenmochi N.
Genome Res. 2002 Mar;12(3):379-90.
PMID 11875025
 
Sequence of a cDNA encoding human ribosomal protein L26 and of a cDNA probably encoding human ribosomal protein L6.
Zaman GJ.
Nucleic Acids Res. 1993 Apr 11;21(7):1673.
PMID 8479925
 
Negative regulation of HDM2 to attenuate p53 degradation by ribosomal protein L26.
Zhang Y, Wang J, Yuan Y, Zhang W, Guan W, Wu Z, Jin C, Chen H, Zhang L, Yang X, He F.
Nucleic Acids Res. 2010 Jun 11. [Epub ahead of print]
PMID 20542919
 
Identification and analysis of over 2000 ribosomal protein pseudogenes in the human genome.
Zhang Z, Harrison P, Gerstein M.
Genome Res. 2002 Oct;12(10):1466-82.
PMID 12368239
 

Citation

This paper should be referenced as such :
Boggs, K ; Kastan, M
RPL26 (ribosomal protein L26)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(6):470-472.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/RPL26ID47470ch17p13.html


Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ]
  Diamond-Blackfan anemia (DBA)


External links

Nomenclature
HGNC (Hugo)RPL26   10327
Cards
AtlasRPL26ID47470ch17p13
Entrez_Gene (NCBI)RPL26  6154  ribosomal protein L26
AliasesDBA11; L26
GeneCards (Weizmann)RPL26
Ensembl hg19 (Hinxton)ENSG00000161970 [Gene_View]  chr17:8280834-8286565 [Contig_View]  RPL26 [Vega]
Ensembl hg38 (Hinxton)ENSG00000161970 [Gene_View]  chr17:8280834-8286565 [Contig_View]  RPL26 [Vega]
ICGC DataPortalENSG00000161970
TCGA cBioPortalRPL26
AceView (NCBI)RPL26
Genatlas (Paris)RPL26
WikiGenes6154
SOURCE (Princeton)RPL26
Genetics Home Reference (NIH)RPL26
Genomic and cartography
GoldenPath hg19 (UCSC)RPL26  -     chr17:8280834-8286565 -  17p13   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)RPL26  -     17p13   [Description]    (hg38-Dec_2013)
EnsemblRPL26 - 17p13 [CytoView hg19]  RPL26 - 17p13 [CytoView hg38]
Mapping of homologs : NCBIRPL26 [Mapview hg19]  RPL26 [Mapview hg38]
OMIM603704   614900   
Gene and transcription
Genbank (Entrez)AK311804 BC066316 BC071664 BI091167 BI596427
RefSeq transcript (Entrez)NM_000987 NM_001315530 NM_001315531
RefSeq genomic (Entrez)NC_000017 NC_018928 NG_031989 NT_010718 NW_004929405
Consensus coding sequences : CCDS (NCBI)RPL26
Cluster EST : UnigeneHs.744896 [ NCBI ]
CGAP (NCI)Hs.744896
Alternative Splicing GalleryENSG00000161970
Gene ExpressionRPL26 [ NCBI-GEO ]   RPL26 [ EBI - ARRAY_EXPRESS ]   RPL26 [ SEEK ]   RPL26 [ MEM ]
Gene Expression Viewer (FireBrowse)RPL26 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6154
GTEX Portal (Tissue expression)RPL26
Protein : pattern, domain, 3D structure
UniProt/SwissProtP61254   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP61254  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP61254
Splice isoforms : SwissVarP61254
PhosPhoSitePlusP61254
Domaine pattern : Prosite (Expaxy)RIBOSOMAL_L24 (PS01108)   
Domains : Interpro (EBI)KOW    Rib_L2_dom2    Ribosomal_L24/26_CS    Ribosomal_L26/L24P_euk/arc    Translation_prot_SH3-like   
Domain families : Pfam (Sanger)KOW (PF00467)    Ribosomal_L26 (PF16906)   
Domain families : Pfam (NCBI)pfam00467    pfam16906   
Domain families : Smart (EMBL)KOW (SM00739)  
Conserved Domain (NCBI)RPL26
DMDM Disease mutations6154
Blocks (Seattle)RPL26
PDB (SRS)4UG0    4V6X    5AJ0   
PDB (PDBSum)4UG0    4V6X    5AJ0   
PDB (IMB)4UG0    4V6X    5AJ0   
PDB (RSDB)4UG0    4V6X    5AJ0   
Structural Biology KnowledgeBase4UG0    4V6X    5AJ0   
SCOP (Structural Classification of Proteins)4UG0    4V6X    5AJ0   
CATH (Classification of proteins structures)4UG0    4V6X    5AJ0   
SuperfamilyP61254
Human Protein AtlasENSG00000161970
Peptide AtlasP61254
HPRD04746
IPIIPI00027270   IPI00433834   
Protein Interaction databases
DIP (DOE-UCLA)P61254
IntAct (EBI)P61254
FunCoupENSG00000161970
BioGRIDRPL26
STRING (EMBL)RPL26
ZODIACRPL26
Ontologies - Pathways
QuickGOP61254
Ontology : AmiGOnuclear-transcribed mRNA catabolic process, nonsense-mediated decay  cytoplasmic translation  RNA binding  structural constituent of ribosome  protein binding  cytosol  rRNA processing  rRNA processing  translation  translational initiation  SRP-dependent cotranslational protein targeting to membrane  membrane  viral transcription  cytosolic large ribosomal subunit  ribosomal large subunit biogenesis  poly(A) RNA binding  extracellular exosome  
Ontology : EGO-EBInuclear-transcribed mRNA catabolic process, nonsense-mediated decay  cytoplasmic translation  RNA binding  structural constituent of ribosome  protein binding  cytosol  rRNA processing  rRNA processing  translation  translational initiation  SRP-dependent cotranslational protein targeting to membrane  membrane  viral transcription  cytosolic large ribosomal subunit  ribosomal large subunit biogenesis  poly(A) RNA binding  extracellular exosome  
Pathways : KEGGRibosome   
REACTOMEP61254 [protein]
REACTOME Pathways156827 [pathway]   156902 [pathway]   1799339 [pathway]   192823 [pathway]   2408557 [pathway]   6791226 [pathway]   72689 [pathway]   72706 [pathway]   72764 [pathway]   975956 [pathway]   975957 [pathway]   
NDEx NetworkRPL26
Atlas of Cancer Signalling NetworkRPL26
Wikipedia pathwaysRPL26
Orthology - Evolution
OrthoDB6154
GeneTree (enSembl)ENSG00000161970
Phylogenetic Trees/Animal Genes : TreeFamRPL26
HOVERGENP61254
HOGENOMP61254
Homologs : HomoloGeneRPL26
Homology/Alignments : Family Browser (UCSC)RPL26
Gene fusions - Rearrangements
Fusion : MitelmanRPL26/ESF1 [17p13.1/20p12.1]  
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerRPL26 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)RPL26
dbVarRPL26
ClinVarRPL26
1000_GenomesRPL26 
Exome Variant ServerRPL26
ExAC (Exome Aggregation Consortium)RPL26 (select the gene name)
Genetic variants : HAPMAP6154
Genomic Variants (DGV)RPL26 [DGVbeta]
DECIPHER (Syndromes)17:8280834-8286565  ENSG00000161970
CONAN: Copy Number AnalysisRPL26 
Mutations
ICGC Data PortalRPL26 
TCGA Data PortalRPL26 
Broad Tumor PortalRPL26
OASIS PortalRPL26 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICRPL26  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDRPL26
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)**PUBLIC** CCHMC Molecular Genetics Laboratory Mutation Database
LOVD (Leiden Open Variation Database)Diamond-Blackfan Anemia
BioMutasearch RPL26
DgiDB (Drug Gene Interaction Database)RPL26
DoCM (Curated mutations)RPL26 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)RPL26 (select a term)
intoGenRPL26
NCG5 (London)RPL26
Cancer3DRPL26(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM603704    614900   
Orphanet429   
MedgenRPL26
Genetic Testing Registry RPL26
NextProtP61254 [Medical]
TSGene6154
GENETestsRPL26
Huge Navigator RPL26 [HugePedia]
snp3D : Map Gene to Disease6154
BioCentury BCIQRPL26
ClinGenRPL26
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6154
Chemical/Pharm GKB GenePA34705
Clinical trialRPL26
Miscellaneous
canSAR (ICR)RPL26 (select the gene name)
Probes
Litterature
PubMed55 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineRPL26
EVEXRPL26
GoPubMedRPL26
iHOPRPL26
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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