Abstract
Telomerase reverse transcriptase (TERT) and the non-coding telomerase RNA subunit (TR) constitute the core of telomerase. Here we now report that the putative F-box protein Pof8 is also a constitutive component of active telomerase in fission yeast. Pof8 functions in a hierarchical assembly pathway by promoting the binding of the Lsm2-8 complex to telomerase RNA, which in turn promotes binding of the catalytic subunit. Loss of Pof8 reduces TER1 stability, causes a severe assembly defect, and results in critically short telomeres. Structure profile searches identified similarities between Pof8 and telomerase subunits from ciliated protozoa, making Pof8 next to TERT the most widely conserved telomerase subunits identified to date.
Highlights
Telomerase reverse transcriptase (TERT) and the non-coding telomerase RNA subunit (TR) constitute the core of telomerase
Telomerase RNA subunits are transcribed as precursors that undergo a series of processing events to produce the mature form that is assembled into the active telomerase complex
We demonstrate that a critical role for La family members in telomerase biogenesis and function is conserved in fission yeast, where telomerase RNA is a pol II transcript
Summary
Telomerase reverse transcriptase (TERT) and the non-coding telomerase RNA subunit (TR) constitute the core of telomerase. It has been thought that proteins involved in the processing and stabilization of pol III transcripts may only function in telomerase RNA biogenesis in ciliates This includes members of the Lupus La antigen-related protein (LARP) family[13], which are components of the telomerase holoenzyme in ciliates and are critical for the assembly, nuclear retention, and activity of telomerase[14,15,16,17,18]. Our results reveal that the Pof[8] protein binds to telomerase RNA, functions in hierarchical assembly by promoting Lsm[2,3,4,5,6,7,8] binding, and forms a constitutive component of the active enzyme. Our findings reveal an ancient role for La-related proteins (LARP) in telomerase biogenesis and indicate that evolutionary conservation in holoenzyme composition extends much further than previously thought
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