The RNA exosome complex constitutes the major nuclear eukaryotic 3'-5' 
exonuclease. Outside of nucleoli, the human nucleoplasmic exosome is directed to 
some of its substrates by the nuclear exosome targeting (NEXT) complex. How NEXT 
targets RNA has remained elusive. Using an in vivo crosslinking approach, we 
report global RNA binding sites of RBM7, a key component of NEXT. RBM7 
associates broadly with RNA polymerase II-derived RNA, including pre-mRNA and 
short-lived exosome substrates such as promoter upstream transcripts (PROMPTs), 
enhancer RNAs (eRNAs), and 3'-extended products from snRNA and 
replication-dependent histone genes. Within pre-mRNA, RBM7 accumulates at the 3' 
ends of introns, and pulse-labeling experiments demonstrate that RBM7/NEXT 
defines an early exosome-targeting pathway for 3'-extended snoRNAs derived from 
such introns. We propose that RBM7 is generally loaded onto newly synthesized 
RNA to accommodate exosome action in case of available unprotected RNA 3' ends.