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Biology subjects

Fahlman, R. P.

Publications and source records attributed to Fahlman, R. P..

2 recordsLinked to original sources

Modifications in the T arm of tRNA globally determine tRNA maturation, function and cellular fitness

All elongator tRNAs harbor 5-methyluridine 54 and pseudouridine 55 in the T arm, which are generated by the enzymes TrmA and TruB, respectively. Escherichia coli TrmA and TruB both act as tRNA chaperones, and strains lacking trmA or truB are outcompeted by wildtype. Here, we investigate how TrmA and TruB contribute to cellular fitness. Deletion of trmA and truB in E. coli causes a global decrease in aminoacylation and alters other tRNA modification such as acp3U47. Whereas overall protein synthesis is not affected in {Delta}trmA and {Delta}truB strains, the translation of a specific subset of codons is significantly impaired, and the expression of many specific proteins is translationally changed. In conclusion, we demonstrate that universal modifications of the tRNA T arm are critical for global tRNA function by enhancing tRNA maturation, tRNA aminoacylation, and translation, thereby improving cellular fitness and explaining trmA and truB conservation.

molecular biology↗

An RNA guanine quadruplex regulated pathway to TRAIL-sensitization by DDX21

DDX21 is a newly discovered RNA G-quadruplex (rG4) binding protein with no known biological rG4 targets. In this study we identified 26 proteins that are expressed at significantly different levels in cells expressing wild type DDX21 relative to an rG4 binding deficient DDX21 (M4). From this list we validate MAGED2 as a protein that is regulated by DDX21 through rG4 in its 5UTR. MAGED2 protein levels, but not mRNA levels, are reduced by half in cells expressing only DDX21 M4. MAGED2 has a repressive effect on TRAIL-R2 expression that is relieved under these conditions, resulting in elevated TRAIL-R2 mRNA and protein in cells expressing only DDX21 M4, and rendering previously resistant cells sensitive to TRAIL mediated apoptosis. Our work identifies the role of DDX21 in regulation at the translational level through biologically relevant rG4 and shows that MAGED2 protein levels are regulated, at least in part, by a rG4 forming potential in their 5UTRs.

biochemistry↗