TERRA transcripts localize at long telomeres to regulate telomerase access to chromosome ends

Area of Science:

• Molecular Biology
• Genetics
• Cell Biology

Background:

• The role of TERRA in regulating telomerase in human cells remains unclear.
• TERRA is known to interact with telomerase, but the mechanism of regulation is not fully understood.

Purpose of the Study:

• To elucidate the function of TERRA in telomerase regulation within human cells.
• To investigate how TERRA transcripts influence telomerase localization and activity at telomeres.

Main Methods:

• Live-cell imaging and super-resolution microscopy were employed to observe TERRA and telomerase dynamics.
• TERRA levels were manipulated using antisense oligonucleotides to assess functional consequences.
• Colocalization studies tracked TERRA and the telomerase RNA subunit (hTR) in the nucleoplasm and at telomeres.

Main Results:

• TERRA colocalizes with hTR in the nucleoplasm and at telomeres throughout the cell cycle.
• TERRA transcripts relocate from their telomere of origin to other chromosome ends during telomere lengthening.
• TERRA depletion led to increased hTR localization and residence time at telomeres, enhancing telomerase activity.

Conclusions:

• Telomeric TERRA transcripts act in trans to inhibit telomere elongation by telomerase.
• TERRA impairs telomerase access to telomeres distinct from their origin, thus regulating telomere length.
• TERRA functions as a negative regulator of telomerase, controlling its access to telomeres.