AN AMINO-ACID-SEQUENCE MOTIF SUFFICIENT FOR SUBNUCLEAR LOCALIZATION OF AN ARGININE SERINE-RICH SPLICING FACTOR

We have identified an amino acid sequence in the Drosophila Transforme r (Tra) protein that is capable of directing a heterologous protein to nuclear speckles, regions of the nucleus previously shown to contain high concentrations of spliceosomal small nuclear RNAs and splicing fa ctors. This sequence contains a nucleoplasmin-like bipartite nuclear l ocalization signal (NLS) and a repeating arginine/serine (RS) dipeptid e sequence adjacent to a short stretch of basic amino acids. Sequence comparisons from a number of other splicing factors that colocalize to nuclear speckles reveal the presence of one or more copies of this mo tif. We propose a two-step subnuclear localization mechanism for splic ing factors. The first step is transport across the nuclear envelope v ia the nucleoplasmin-like NLS, while the second step is association wi th components in the speckled domain via the RS dipeptide sequence.