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Vol. 13, Issue 9, 3192-3202, September 2002



and
§
*Bloomfield Centre for Research in Aging, Lady Davis Institute for
Medical Research, Sir Mortimer B. Davis-Jewish General Hospital,
Montréal, Québec, H3T 1E2, Canada; Telomerase is a ribonucleoprotein (RNP) complex that is minimally
composed of a protein catalytic subunit, the telomerase reverse
transcriptase (TERT), and an RNA component, the telomerase RNA. The
survival of motor neuron (SMN) gene codes
for a protein involved in the biogenesis of certain RNPs. Here, we
report that SMN is a telomerase-associated protein. Using in vitro
binding assays and immunoprecipitation experiments, we demonstrate an association between SMN and the telomerase RNP in vitro and in human
cells. The specific immunopurification of SMN from human 293 cells
copurified telomerase activity, suggesting that SMN associates with a
subset of the functional telomerase holoenzyme. Our results also
indicate that the human telomerase RNA and the human (h) TERT are not
associated with Sm proteins, in contrast to Saccharomyces
cerevisiae telomerase. Immunofluorescence analysis showed that
hTERT does not specifically colocalize with wild-type SMN in gems or
Cajal bodies. However, a dominant-negative mutant of SMN (SMN
Department
of Anatomy and Cell Biology, McGill University, Montréal,
Québec, H3A 2B2, Canada; and
Terry Fox Molecular
Oncology Group and Departments of Oncology, Medicine, and Microbiology
and Immunology, McGill University, Montréal, Québec, H3A
2B2, Canada
N27)
previously characterized to elicit the cellular reorganization of small
nuclear RNPs caused the accumulation of hTERT in specific
SMN
N27-induced cellular bodies. Furthermore, coexpression of
SMN
N27 and hTERT in rabbit reticulocyte lysates decreased the
efficiency of human telomerase reconstitution in vitro. Our results
establish SMN as a novel telomerase-associated protein that is likely
to function in human telomerase biogenesis.
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