Abstract: This invention provides a method of modulating translation termination efficiency of mRNA and/or promoting degradation of abberant transcripts. Also, this invention provides a method of screening for a drug active involved in enhancing translation termination and a method for identifying a disease state involving defective the protein complex. This invention provides a purified complex comprising an amount of a human Upf1p protein, a peptidyl eucaryotic release factor 1 (eRF1) and a peptidyl eucaryotic release factor 3 (eRF3) effective to modulate translation termination. Further, this invention provides an expression vector which comprises a nucleic acid encoding a human Upf1p protein, a peptidyl eucaryotic release factor 1 (eRF1) and a peptidyl eucaryotic release factor 3 (eRF3) operably linked to a regulatory element.