RNA processing protein complexes and uses thereof

Abstract

The invention provides human protein complexes with endonuclease activity. In particular, the invention provides human protein complexes with tRNA splicing endonuclease activity and/or 3' end pre-mRNA endonuclease activity. The invention also provides a splice variant of human Sen2, namely human Sen2deltaEx8, and human protein complexes comprising human Sen2deltaEx8. The human Sen2deltaEx8 complexes have pre-tRNA cleavage activity and/or 3' end pre-mRNA endonuclease activity. The invention also provides human protein complexes with pre-ribosomal RNA cleavage activity. The invention also provides antibodies that immunospecifically bind to a complex described herein or a component thereof, and methods of diagnosing, preventing, treating, managing or ameliorating a disorder utilizing such antibodies. The present invention also provides methods utilizing the complexes described herein, inter alia, in screening, diagnosis, and therapy. The invention further provides methods of preparing and purifying the complexes. The present invention further provides methods of identifying a compound that modulates the expression of a component of a complex described herein, the formation of a complex described herein or the activity of a complex described herein, and methods of preventing, treating, managing or ameliorating a disorder, such as a proliferative disorder, or a symptom thereof utilizing a compound identified in accordance with the methods.

Description

[0001] This application claims the benefit of U.S. Provisional Application Ser. No. 60 / 484,615, filed Jul. 2, 2003, the entire disclosure of which is incorporated by reference herein in its entirety.1. INTRODUCTION[0002] The invention provides human protein complexes with endonuclease activity. In particular, the invention provides human protein complexes with tRNA splicing endonuclease activity and / or 3' end pre-mRNA endonuclease activity. The invention also provides a splice variant of human Sen2, namely human Sen2deltaEx8, and human protein complexes comprising human Sen2deltaEx8. The human Sen2deltaEx8 complexes have RNA-nucleolytic activity. The invention also provides human protein complexes with pre-ribosomal RNA cleavage activity. The invention also provides antibodies that immunospecifically bind to a complex described herein or a component thereof, and methods of diagnosing, preventing, treating, managing or ameliorating a disorder utilizing such antibodies. The present in...

AI Technical Summary

Benefits of technology

0056] A compound identified in the assays described herein that modulates the expression of a component of a complex of the invention, the formation of a complex of the invention, the RNA-nucleolytic activity of a complex of the invention (e.g., the pre-tRNA splicing endonuclease activity, the 3' end pre-mRNA endonuclease activity, the pre-tRNA cleavage activity of a complex of the invention, and/or the pre-ribosomal RNA cleavage activity of a complex of the invention) may be tested in in vitro assays (e.g., cell-based assays or cell-free assays) and/or in vivo assays well-known to one of skill in the art or described herein for the effect of the compound a disorder described herein (e.g., a proliferative disorder or a disorder characterized by, associated with or caused by abnormal RNA-nucleolytic activity) or on cells from a patient with a particular disorder.

0057] In a specific embodiment, a compound identified in the assays described herein that inhibits or reduces the expression of a component of a complex of the invention, the formation of a complex of the invention, the RNA-nucleolytic activity of a complex of the invention (e.g., the pre-tRNA splicing endonuclease activity, the 3' end pre-mRNA endonuclease activity, the pre-tRNA cleavage activity of a complex of the invention, and/or the pre-ribosomal RNA cleavage activity of a complex of the invention) may be tested in in vitro assays (e.

Problems solved by technology

All of these approaches pose significant drawbacks for the patient.

Surgery, for example, can be contraindicated due to the health of the patient or can be unacceptable to the patient.

Additionally, surgery might not completely remove the neoplastic tissue.

Radiation therapy is effective only when the irradiated neoplastic tissue exhibits a higher sensitivity to radiation than normal tissue, and radiation therapy can also often elicit seriou

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