Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

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AB001


ABSTRACT: Diamond-Blackfan anemia (DBA) is a congenital disorder that results predominantly from mutations in various ribosomal protein genes. In order to determine how these mutations affect the translation of specific mRNAs, we performed microarray analysis of polysomal transcripts isolated from lymphoblast cells derived from DBA patients carrying different haploinsufficient mutations in either RPS19 or RPL11. One of the few overlapping transcripts that we found significantly decreased on the polysomes codes for branched-chain aminotransferase-1 (BCAT-1). We go on to determine that translation of BCAT-1 is especially impaired in cells carrying mutations in the small ribosomal protein genes, and provide evidence that this effect is due to its unusually long 5M-bM-^@M-^YUTR. The BCAT-1 enzyme is critical for synthesis of the branched-chain amino acids, including leucine. It is known that DBA patients respond well to orally administered leucine, and large-scale clinical trials as such are currently underway. Our results suggest that the haploinsufficient loss of ribosomal protein genes results in a decrease of BCAT-1 translation and provide an explanation for why leucine administration is beneficial for DBA patients. In this expression study duplicate mRNA samples were generated from polysomes isolated from celllines with mutations in RPS19 or RPL11 or normal controls. In each group 3 cellines were tested. Duplicate samples were analyzed in dyeswap. As common reference the commercial universal human reference RNA (Stratagene) was used.

ORGANISM(S): Homo sapiens

SUBMITTER: Marian Groot Koerkamp 

PROVIDER: E-GEOD-43117 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Translation of branched-chain aminotransferase-1 transcripts is impaired in cells haploinsufficient for ribosomal protein genes.

Pereboom Tamara C TC   Bondt Albert A   Pallaki Paschalina P   Klasson Tim D TD   Goos Yvonne J YJ   Essers Paul B PB   Groot Koerkamp Marian J A MJ   Gazda Hanna T HT   Holstege Frank C P FC   Costa Lydie Da LD   MacInnes Alyson W AW  

Experimental hematology 20140123 5


Diamond-Blackfan anemia (DBA) is a bone marrow failure syndrome linked to mutations in ribosomal protein (RP) genes that result in the impaired proliferation of hematopoietic progenitor cells. The etiology of DBA is not completely understood; however, the ribosomal nature of the genes involved has led to speculation that these mutations may alter the landscape of messenger RNA (mRNA) translation. Here, we performed comparative microarray analysis of polysomal mRNA transcripts isolated from lymph  ...[more]

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