The yeast homolog of human PinX1 is involved in rRNA and small nucleolar RNA maturation, not in telomere elongation inhibition.
In human cells, PinX1 protein has recently been shown to regulate telomere length by repressing the telomerase. In this work, we show that the putative yeast homolog of PinX1, encoded by the YGR280c open reading frame (ORF), is a new component of the ribosomal RNA processing machinery. The protein has a KK(E/D) C-terminal domain typical of nucleolar proteins and bears a putative RNA interacting domain widespread in eukaryotes called the G-patch. The protein was hence renamed Gno1p (G-patch nucleolar protein). GNO1 deletion results in a large growth defect due to the inhibition of the pre-ribosomal RNA processing first cleavage steps at sites A(0), A(1), and A(2). Furthermore, Gno1p is involved in the final 3'-end trimming of U18 and U24 small nucleolar RNAs. A mutational analysis showed that the G-patch of Gno1p is essential for both functions, whereas the KK(E/D) repeats are only required for U18 small nucleolar RNA maturation. We found that PinX1 complemented the gno1-Delta mutation, suggesting that it has a dual function in telomere length regulation and ribosomal RNA maturation in agreement with its telomeric and nucleolar localization in human cells. Conversely, we found that Gno1p does not exhibit the in vivo telomerase inhibitor activity of PinX1.
Guglielmi
Benjamin
B
Service de Biochimie et Génétique Moléculaire, Bâtiment 144, Commissariat à l'Energie Atomique/Saclay, F-91191 Gif-sur-Yvette Cedex, France.
Werner
Michel
M
D000595:Amino Acid Sequence; D001483:Base Sequence; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D017931:DNA Primers; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011401:Promoter Regions, Genetic; D012335:RNA, Ribosomal / Q000378:metabolism*; D012342:RNA, Small Nuclear / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development; D017386:Sequence Homology, Amino Acid; D016615:Telomere; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; D017931:DNA Primers; C440808:PINX1 protein, human; D012335:RNA, Ribosomal; D012342:RNA, Small Nuclear; D025521:Tumor Suppressor Proteins