Abstract
Telomere length is regulated mostly by proteins directly associated with telomeres. However, genome-wide analysis of Saccharomyces cerevisiae mutants has revealed that deletion of Hpr1p, a component of the THO complex, also affects telomere length. The THO complex comprises four protein subunits, namely, Tho2p, Hpr1p, Mft1p, and Thp2p. These subunits interplay between transcription elongation and co-transcriptional assembly of export-competent mRNPs. Here we found that the deletion of tho2 or hpr1 caused telomere lengthening by ∼50–100 bps, whereas that of mft1 or thp2 did not affect telomere length. Since the THO complex functions in transcription elongation, we analyzed the expression of telomere-associated proteins in mutants depleted of complex components. We found that both the mRNA and protein levels of RIF1 were decreased in tho2 and hpr1 cells. RIF1 encodes a 1917-amino acid polypeptide that is involved in regulating telomere length and the formation of telomeric heterochromatin. Hpr1p and Tho2p appeared to affect telomeres through Rif1p, as increased Rif1p levels suppressed the telomere lengthening in tho2 and hpr1 cells. Moreover, yeast cells carrying rif1 tho2 or rif1 hpr1 double mutations showed telomere lengths and telomere silencing effects similar to those observed in the rif1 mutant. Thus, we conclude that mutations of components of the THO complex affect telomere functions by reducing the expression of a telomere-associated protein, Rif1p.
Highlights
Telomeres are the structure at the ends of eukaryotic linear chromosomes [1,2]
Mutations of the other two THO complex components, MFT1 and THP2, did not affect telomere length (Fig. 1A), it has been reported that mutations of these two genes cause slightly shorter telomeres [31]
RIF1 expression is reduced in hpr1 and tho2 cells we explored the mechanism by which HPR1 and THO2 affect telomere length
Summary
Telomeres are the structure at the ends of eukaryotic linear chromosomes [1,2]. They are essential for the maintenance of chromosome integrity, and protect natural DNA ends from being recognized as double-strand breaks. The telomeric DNA is composed of short, tandemly repeated sequences with a strand rich in guanine residues (G-strand) running 59 to 39 toward the end of the telomere. The telomeric sequences in the brewer’s yeast Saccharomyces cerevisiae are ,250–300 base pair-long TG1–3/C1–3A repeats. Telomerase is a ribonucleoprotein containing a catalytic protein component TERT (telomerase reverse transcriptase) and an associated RNA moiety, TER, which serves as the template to extend telomeric DNA sequences. In S. cerevisiae, these two components are encoded by EST2 [4,5] and TLC1 [6], respectively
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