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bioRxiv · 10.1101/739532

Structure of S. pombe telomerase protein Pof8 C-terminal domain is an xRRM conserved among LARP7 proteins

Basu, R.·Eichhorn, C. D.·Cheng, R.·Feigon, J.
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Abstract

La related proteins group 7 (LARP7) are a class of RNA chaperones that bind the 3ends of RNA and are constitutively associated with their specific target RNAs. In metazoa, Larp7 binds to the long non-coding 7SK RNA as a core component of the 7SK RNP, a major regulator of eukaryotic transcription. In ciliates, a LARP7 protein (p65 in Tetrahymena) is a core component of telomerase, an essential ribonucleoprotein complex that maintains the DNA length at eukaryotic chromosome ends. p65 is important for the ordered assembly of telomerase RNA (TER) with telomerase reverse transcriptase (TERT). Although a LARP7 as a telomerase holoenzyme component was initially thought to be specific to ciliate telomerases, Schizosaccharomyces pombe Pof8 was recently identified as a LARP7 protein and a core component of fission yeast telomerase essential for biogenesis. There is also evidence that human Larp7 associates with telomerase. LARP7 proteins have conserved N-terminal La motif and RRM1 (La module) and C-terminal RRM2 with specific RNA substrate recognition attributed to RRM2, first structurally characterized in p65 as an atypical RRM named xRRM. Here we present the X-ray crystal structure and NMR studies of S. pombe Pof8 RRM2. Sequence and structure comparison of Pof8 RRM2 to p65 and hLarp7 xRRMs reveals conserved features for RNA binding with the main variability in the length of the non-canonical helix 3. This study shows that Pof8 has conserved xRRM features, providing insight into TER recognition and the defining characteristics of the xRRM.\n\nHighlightsO_LIThe structure of the S. pombe LARP7 Pof8 C-terminal domain is an xRRM.\nC_LIO_LICiliates, human, and fission yeast contain LARP7 proteins with xRRMs involved in telomerase biogenesis.\nC_LIO_LIWith three examples of xRRM structures, we refine the definition of xRRM.\nC_LI

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Basu, R., Eichhorn, C. D., Cheng, R., Feigon, J.. 2019-08-19. Structure of S. pombe telomerase protein Pof8 C-terminal domain is an xRRM conserved among LARP7 proteins. https://doi.org/10.1101/739532

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