Characterization of U2AF6, a Splicing Factor Related to U2AF35

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American Society for Microbiology

RESUMO

The essential splicing factor U2AF (U2 auxiliary factor) is a heterodimer composed of 65-kDa (U2AF65) and 35-kDa (U2AF35) subunits. U2AF35 has multiple functions in pre-mRNA splicing. First, U2AF35 has been shown to function by directly interacting with the AG at the 3′ splice site. Second, U2AF35 is thought to play a role in the recruitment of U2AF65 by serine-arginine-rich (SR) proteins in enhancer-dependent splicing. It has been proposed that the physical interaction between the arginine-serine-rich (RS) domain of U2AF35 and SR proteins is important for this activity. However, other data suggest that this may not be the case. Here, we report the identification of a mammalian gene that encodes a 26-kDa protein bearing strong sequence similarity to U2AF35, designated U2AF26. The N-terminal 187 amino acids of U2AF35 and U2AF26 are nearly identical. However, the C-terminal domain of U2AF26 lacks many characteristics of the U2AF35 RS domain and, therefore, might be incapable of interacting with SR proteins. We show that U2AF26 can associate with U2AF65 and can functionally substitute for U2AF35 in both constitutive and enhancer-dependent splicing, demonstrating that the RS domain of the small U2AF subunit is not required for splicing enhancer function. Finally, we show that U2AF26 functions by enhancing the binding of U2AF65 to weak 3′ splice sites. These studies identify U2AF26 as a mammalian splicing factor and demonstrate that distinct U2AF complexes can participate in pre-mRNA splicing. Based on its sequence and functional similarity to U2AF35, U2AF26 may play a role in regulating alternative splicing.

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