tRNA modification dynamics from individual organisms to metaepitranscriptomics of microbiomes

FtsJ RNA 2′-O-methyltransferase 1 (FTSJ1) gene has been implicated in X-linked intellectual disability (XLID), but the molecular pathogenesis is unknown. We show that Ftsj1 is responsible for 2′-O-methylation of 11 species of cytosolic transfer RNAs (tRNAs) at the anticodon region, and these modifications are abolished in Ftsj1 knockout (KO) mice and XLID patient–derived cells. Loss of 2′-O-methylation in Ftsj1 KO mouse selectively reduced the steady-state level of tRNAPhe in the brain, resulting in a slow decoding at Phe codons. Ribosome profiling showed that translation efficiency is significantly reduced in a subset of genes that need to be efficiently translated to support synaptic organization and functions. Ftsj1 KO mice display immature synaptic morphology and aberrant synaptic plasticity, which are associated with anxiety-like and memory deficits. The data illuminate a fundamental role of tRNA modification in the brain through regulation of translation efficiency and provide mechanistic insights into FTSJ1-related XLID.

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Fluorimetric Study of the Complex between Yeast Phenylalanyl-tRNA Synthetase and tRNAPhe. 1. Changes in the Conformation of the Enzyme and tRNA; Modification of the Wybutine Neighbourhood

European Journal of Biochemistry ◽

10.1111/j.1432-1033.1980.tb04298.x ◽

1980 ◽

Vol 103 (1) ◽

pp. 145-153 ◽

Cited By ~ 43

Author(s):

Ricardo EHRLICH ◽

Jean-Francois LEFEVRE ◽

Pierre REMY

Keyword(s):

Trna Synthetase ◽

Trna Modification

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An early step in wobble uridine tRNA modification requires the Elongator complex

RNA ◽

10.1261/rna.7247705 ◽

2005 ◽

Vol 11 (4) ◽

pp. 424-436 ◽

Cited By ~ 289

Author(s):

B. HUANG

Keyword(s):

Trna Modification ◽

Early Step ◽

Elongator Complex

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A Novel Gene Involved in the Survival of Streptococcus mutans under Stress Conditions

Applied and Environmental Microbiology ◽

10.1128/aem.02549-13 ◽

2013 ◽

Vol 80 (1) ◽

pp. 97-103 ◽

Cited By ~ 11

Author(s):

Dan Li ◽

Yukie Shibata ◽

Toru Takeshita ◽

Yoshihisa Yamashita

Keyword(s):

Streptococcus Mutans ◽

Streptococcus Pyogenes ◽

Biofilm Formation ◽

Acid Tolerance ◽

Stress Conditions ◽

Insertion Mutagenesis ◽

Trna Modification ◽

Content Type ◽

Virulence Proteins ◽

Random Insertion

ABSTRACTAStreptococcus mutansmutant defective in aciduricity was constructed by random-insertion mutagenesis. Sequence analysis of the mutant revealed a mutation ingidA, which is known to be involved in tRNA modification inStreptococcus pyogenes. Complementation ofgidAbyS. pyogenesgidArecovered the acid tolerance ofS. mutans. Although thegidA-inactivatedS. pyogenesmutant exhibited significantly reduced expression of multiple extracellular virulence proteins, theS. mutansmutant did not. On the other hand, thegidAmutant ofS. mutansshowed reduced ability to withstand exposure to other stress conditions (high osmotic pressure, high temperature, and bacitracin stress) besides an acidic environment. In addition, loss of GidA decreased the capacity for glucose-dependent biofilm formation by over 50%. This study revealed thatgidAplays critical roles in the survival ofS. mutansunder stress conditions, including lower pH.

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