Long noncoding RNAs (lncRNAs) and mRNAs share many features, including 5′-methylguanosine caps and poly(A) tails, and both are transcribed by RNA polymerase II (Pol II). However, most lncRNAs are retained in the nucleus, whereas almost all mRNAs are exported to the cytoplasm, suggesting that their RNA maturation paths diverge at some point. All transcripts interact with a series of protein factors during their maturation, thus forming ribonucleoprotein particles (RNPs). Tuck and Tollervey therefore analyzed the in vivo, transcriptome-wide targets of 13 RNA-processing, export and turnover factors in budding yeast, using the cross-linking and analysis of cDNA (CRAC) technique, to produce a transcriptome-wide survey of RNP composition. Comparison of the maturation pathways of mRNAs and the stable unannotated transcript (SUT) and cryptic unstable transcript (CUT) classes of lncRNAs revealed that transcript fate is largely determined during 3′-end formation. Whereas mRNAs and SUTs carried the hallmarks of cleavage and polyadenylation, these were absent from CUTs, which undergo rapid degradation in the nucleus. The RNP composition of SUTs overlapped significantly with that of mRNAs, with some SUTs being retained in the nucleus while others were exported to the cytoplasm. Moreover, about 10% of mRNAs behaved like lncRNAs, being retained and degraded in the nucleus. The extensive heterogeneity in mRNP composition, combined with gene ontology–term analyses, led the authors to suggest that an mRNA's tailored mRNP composition may be linked to the function of the encoded protein. Nuclear surveillance factors were found to bind promoter-proximal lncRNAs generated by early transcription termination, which occurred to some extent for most mRNAs and could reflect a checkpoint in Pol II transcription. Whether these early-terminating transcripts are functional remains to be determined. This transcriptome-wide survey of RNP composition allows for an RNP-based classification of transcripts, which reflects their regulation and possible function. (Cell 154, 996–1009, 2013)