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Conserved N-terminal motifs of telomerase reverse transcriptase required for ribonucleoprotein assembly in vivo.

TitleConserved N-terminal motifs of telomerase reverse transcriptase required for ribonucleoprotein assembly in vivo.
Publication TypeJournal Article
Year of Publication2003
AuthorsBosoy D, Peng Y, I Mian S, Lue NF
JournalJ Biol Chem
Volume278
Issue6
Pagination3882-90
Date Published2003 Feb 07
ISSN0021-9258
KeywordsAmino Acid Motifs, Amino Acid Sequence, Base Sequence, Catalysis, DNA Primers, DNA-Binding Proteins, Molecular Sequence Data, Ribonucleoproteins, RNA, Sequence Homology, Amino Acid, Telomerase
Abstract

Telomerase is a ribonucleoprotein (RNP) reverse transcriptase responsible for the maintenance of one strand of the telomere terminal repeats. The key protein subunit of the telomerase complex, known as TERT, possesses reverse transcriptase (RT)-like motifs that directly mediate nucleotide addition. The RT motifs are located in the C-terminal region of the polypeptide. Sequence alignments also revealed the existence of four conserved motifs (named GQ, CP, QFP, and T) in the N-terminal region of TERT. The GQ motif of yeast TERT has been demonstrated previously to be essential for telomerase catalysis and may participate in RNP formation. In this report, we show that substitution of conserved residues in the CP, QFP, and T motifs of yeast TERT also impairs both telomere maintenance and telomerase activity, thus confirming the validity of the sequence alignment. The extent of telomere shortening correlates with the extent of reduction in the level of telomerase activity, TERT protein, and TERT-associated TLC1 RNA. Overexpression of the mutant proteins does not result in telomere shortening, implying that assembly rather than catalytic function was affected. This notion was further supported by comparing the efficiency of RNP formation in the wild type and the overexpression strains. Taken together, our results show that three of the four N-terminal motifs are required for efficient telomerase RNP formation in vivo but not for the enzymatic function of telomerase. We also show that the majority of telomerase-associated TLC1 RNA has a more upstream 3' end than previously reported, consistent with additional processing events during RNP maturation.

DOI10.1074/jbc.M210645200
Alternate JournalJ Biol Chem
PubMed ID12458198
Grant ListR01 GM62631-02 / GM / NIGMS NIH HHS / United States

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