Nicholas K Conrad ¹, and Joan A Steitz ^1, *

¹ Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University, New Haven, CT, USA

* To whom correspondence should be addressed. E-mail:   joan.steitz@yale.edu

The Kaposi's sarcoma-associated herpesvirus produces a 1077 nucleotide noncoding, polyadenylated, exclusively nuclear RNA called PAN that is highly expressed in lytically infected cells. We report that PAN contains a novel post-transcriptional element essential for its abundant accumulation. The element, PAN-ENE (PAN RNA expression and nuclear retention element), increases the efficiency of 3'-end formation in vivo and is sufficient to enhance RNA abundance from an otherwise inefficiently expressed intronless ^b-globin construct. The PAN-ENE does not concomitantly increase the production of encoded protein. Rather, it retains the unspliced ^b-globin mRNA in the nucleus. Tethering of export factors can override the nuclear retention of the PAN-ENE, supporting a mechanism whereby the PAN-ENE blocks assembly of an export-competent mRNP. The activities of the PAN-ENE are specific to intronless constructs, since inserting the PAN-ENE into a spliced ^b-globin construct has no effect on mRNA abundance and does not affect localization. This is the first characterization of a cis-acting element that increases RNA abundance of intronless transcripts but inhibits assembly of an export-competent mRNP.

Additional References:

1. Blower MD, Nachury M, Heald R, and Weis K, "A Rae1-Containing Ribonucleoprotein Complex Is Required for Mitotic Spindle Assembly".

2. Sallacz NB,  and Jantsch MF,  "Chromosomal Storage of the RNA-editing Enzyme ADAR1 in Xenopus Oocytes".

3. Cheng J, Kapranov P, Drenkow J, Dike S, Brubaker S, Patel S, Long J, Stern D, Tammana H, Helt G, Sementchenko V, Piccolboni A, Bekiranov S, Bailey DK, Ganesh M, Ghosh S, Bell I, Gerhard DS, and Gingeras TR, "Transcriptional Maps of 10 Human Chromosomes at 5-Nucleotide Resolution".

4. Kiyosawa H, Mis N, Iwase S, Hayashizaki Y,  and Abe K, "Disclosing hidden transcripts: Mouse natural sense-antisense transcripts tend to be poly(A) negative and nuclear localized".

5. Storz G, Altuvia S, and Wassarman KM, "An Abundance of RNA Regulators".

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