LARP7 family proteins have conserved function in telomerase assembly

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• Telomere maintenance is critical for cellular stability and preventing diseases.
• Telomerase, the enzyme responsible for telomere elongation, requires specific regulatory factors for its biogenesis.
• Understanding these factors is key to developing therapeutic strategies targeting telomerase activity.

Purpose of the Study:

• To identify and characterize novel factors involved in telomerase biogenesis in fission yeast.
• To elucidate the role of the conserved LARP7 family in telomere maintenance.
• To investigate the interaction of Lar7 with telomerase components.

Main Methods:

• Identification of fission yeast Lar7 as a member of the LARP7 family.
• Analysis of RNA-recognition motifs in Lar7 and their binding to telomerase RNA.
• Assessment of Lar7's role in stabilizing telomerase complex formation and localization.
• Comparative analysis with homologous proteins like Tetrahymena p65 and human LARP7.

Main Results:

• Fission yeast Lar7 possesses conserved RNA-recognition motifs that bind telomerase RNA.
• Lar7 protects telomerase RNA from exosomal degradation.
• Lar7 stabilizes the association of telomerase RNA with the LSm2-8 complex and telomerase reverse transcriptase.
• Lar7 is essential for telomerase localization to the telomere and is part of the mature telomerase complex.

Conclusions:

• Lar7 is a crucial factor in fission yeast telomerase biogenesis and function.
• The LARP7 family represents a conserved mechanism for telomere maintenance across species.
• Targeting Lar7 or related proteins could offer new avenues for therapeutic intervention in diseases associated with telomere dysfunction.