RPL26 (ribosomal protein L26)

2010-09-01   Kristy Boggs , Michael Kastan 

Department of Oncology, St Jude Childrens Research Hospital, Memphis, TN 38105, USA

Identity

HGNC
LOCATION
17p13.1
IMAGE
Atlas Image
LOCUSID
ALIAS
DBA11,L26
FUSION GENES

DNA/RNA

Note

Human RPL26 cDNA was derived from mRNA isolated from human non-small cell lung cancer cell line SW-1573.
Atlas Image
RPL26 gene. Exons are represented by boxes (red corresponds to the 5 and 3UTR; 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.

Proteins

Atlas Image
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 5UTR 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 5UTR of p53 mRNA but also the 3UTR. The interaction between complimentary sequences found within the 5 and 3UTR 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 5-3UTR 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.

Implicated in

Bibliography

Pubmed IDLast YearTitleAuthors
114899482001Point mutation in essential genes with loss or mutation of the second allele: relevance to the retention of tumor-specific antigens.Beck-Engeser GB et al
199439452009Ribosomal protein mRNAs are translationally-regulated during human dendritic cells activation by LPS.Ceppi M et al
2083765620105'-3'-UTR interactions regulate p53 mRNA translation and provide a target for modulating p53 induction after DNA damage.Chen J et al
125662482003Identification of multiple differentially expressed messenger RNAs in normal and pathological trophoblast.Durand S et al
13488621992Genetic transfer of non-P-glycoprotein-mediated multidrug resistance (MDR) in somatic cell fusion: dissection of a compound MDR phenotype.Eijdems EW et al
189510862008Mdm2 regulates p53 mRNA translation through inhibitory interactions with ribosomal protein L26.Ofir-Rosenfeld Y et al
186979202008The role of human ribosomal proteins in the maturation of rRNA and ribosome production.Robledo S et al
162132122005Regulation of p53 translation and induction after DNA damage by ribosomal protein L26 and nucleolin.Takagi M et al
118750252002The human ribosomal protein genes: sequencing and comparative analysis of 73 genes.Yoshihama M et al
84799251993Sequence of a cDNA encoding human ribosomal protein L26 and of a cDNA probably encoding human ribosomal protein L6.Zaman GJ et al
205429192010Negative regulation of HDM2 to attenuate p53 degradation by ribosomal protein L26.Zhang Y et al
123682392002Identification and analysis of over 2000 ribosomal protein pseudogenes in the human genome.Zhang Z et al

Other Information

Locus ID:

NCBI: 6154
MIM: 603704
HGNC: 10327
Ensembl: ENSG00000161970

Variants:

dbSNP: 6154
ClinVar: 6154
TCGA: ENSG00000161970
COSMIC: RPL26

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000161970ENST00000578812J3QQV1
ENSG00000161970ENST00000582485J3QRC4
ENSG00000161970ENST00000582556P61254
ENSG00000161970ENST00000583011P61254
ENSG00000161970ENST00000584164P61254
ENSG00000161970ENST00000584343J3QRI7
ENSG00000161970ENST00000584441J3KS10
ENSG00000161970ENST00000584906J3KSS0
ENSG00000161970ENST00000648839P61254

Expression (GTEx)

0
500
1000
1500

Pathways

PathwaySourceExternal ID
RibosomeKEGGko03010
RibosomeKEGGhsa03010
Ribosome, eukaryotesKEGGhsa_M00177
Ribosome, eukaryotesKEGGM00177
Metabolism of proteinsREACTOMER-HSA-392499
TranslationREACTOMER-HSA-72766
Eukaryotic Translation InitiationREACTOMER-HSA-72613
Cap-dependent Translation InitiationREACTOMER-HSA-72737
Formation of a pool of free 40S subunitsREACTOMER-HSA-72689
GTP hydrolysis and joining of the 60S ribosomal subunitREACTOMER-HSA-72706
L13a-mediated translational silencing of Ceruloplasmin expressionREACTOMER-HSA-156827
SRP-dependent cotranslational protein targeting to membraneREACTOMER-HSA-1799339
Eukaryotic Translation ElongationREACTOMER-HSA-156842
Peptide chain elongationREACTOMER-HSA-156902
Eukaryotic Translation TerminationREACTOMER-HSA-72764
DiseaseREACTOMER-HSA-1643685
Infectious diseaseREACTOMER-HSA-5663205
Influenza InfectionREACTOMER-HSA-168254
Influenza Life CycleREACTOMER-HSA-168255
Influenza Viral RNA Transcription and ReplicationREACTOMER-HSA-168273
Viral mRNA TranslationREACTOMER-HSA-192823
Gene ExpressionREACTOMER-HSA-74160
Nonsense-Mediated Decay (NMD)REACTOMER-HSA-927802
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)REACTOMER-HSA-975957
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)REACTOMER-HSA-975956
MetabolismREACTOMER-HSA-1430728
Metabolism of amino acids and derivativesREACTOMER-HSA-71291
Selenoamino acid metabolismREACTOMER-HSA-2408522
Selenocysteine synthesisREACTOMER-HSA-2408557
rRNA processingREACTOMER-HSA-72312
Major pathway of rRNA processing in the nucleolus and cytosolREACTOMER-HSA-6791226
rRNA processing in the nucleus and cytosolREACTOMER-HSA-8868773

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
189510862008Mdm2 regulates p53 mRNA translation through inhibitory interactions with ribosomal protein L26.113
224311042012Frameshift mutation in p53 regulator RPL26 is associated with multiple physical abnormalities and a specific pre-ribosomal RNA processing defect in diamond-blackfan anemia.58
224338722012Interactions of nucleolin and ribosomal protein L26 (RPL26) in translational control of human p53 mRNA.32
228689292012Silencing expression of ribosomal protein L26 and L29 by RNA interfering inhibits proliferation of human pancreatic cancer PANC-1 cells.15
266870662015The Six1 oncoprotein downregulates p53 via concomitant regulation of RPL26 and microRNA-27a-3p.15
282889922017Identification of a DNA Damage-Induced Alternative Splicing Pathway That Regulates p53 and Cellular Senescence Markers.13
278251412016p73 expression is regulated by ribosomal protein RPL26 through mRNA translation and protein stability.7

Citation

Kristy Boggs ; Michael Kastan

RPL26 (ribosomal protein L26)

Atlas Genet Cytogenet Oncol Haematol. 2010-09-01

Online version: http://atlasgeneticsoncology.org/gene/47470/rpl26