Editorial Note: The Signal Sequence Coding Region Promotes Nuclear Export of mRNA

Concerns were raised that results and conclusions reported in this article [1] are unreliable based on findings reported in subsequent publications. The PLOS Biology Editors reviewed this matter and concluded that the experiments and data reported in [1] were in line with 2007 standards and remain scientifically valid, although the hypothesis and interpretation of the results reported in [1], including in the title, are no longer fully supported given knowledge that has since come to light [2–4], including evidence that some DNA reporter constructs had limitations [2]. The first and corresponding authors stated that the main conclusion, that GC-rich elements, such as the signal-sequence coding region, promote nuclear export of intronless mRNAs, remains valid and is supported by subsequent studies [5–6]. PLOS Biology stands by the article, but cautions readers not to rely on the conclusion expressed in the title, and to interpret the reported results in the context of current knowledge about mechanisms of mRNA export regulation. Additionally, the corresponding author confirmed that Fig S6 is incorrect and is a duplicate of Fig S5, but stated that the original image underlying Fig S6, which the authors submitted to the journal at the time, is no longer available. PLOS considers that the results presented in Fig S6 are supported by other figures and do not significantly impact the overall conclusions of the article. The authors regret that the original data are no longer available. References - 1. Palazzo AF, Springer M, Shibata Y, Lee C-S, Dias AP, Rapoport TA. The signal sequence coding region promotes nuclear export of mRNA. PLoS Biol. 2007;5(12):e322. pmid:18052610 - 2. Lee ES, Akef A, Mahadevan K, Palazzo AF. The consensus 5’ splice site motif inhibits mRNA nuclear export. PLoS One. 2015;10(3):e0122743. pmid:25826302 - 3. Akef A, Zhang H, Masuda S, Palazzo AF. Trafficking of mRNAs containing ALREX-promoting elements through nuclear speckles. Nucleus. 2013;4(4):326–40. pmid:23934081 - 4. Palazzo AF, Lee ES. Sequence Determinants for Nuclear Retention and Cytoplasmic Export of mRNAs and lncRNAs. Front Genet. 2018;9:440. pmid:30386371 - 5. Mordstein C, Savisaar R, Young RS, Bazile J, Talmane L, Luft J, et al. Codon Usage and Splicing Jointly Influence mRNA Localization. Cell Syst. 2020;10(4):351-362.e8. pmid:32275854 - 6. Zuckerman B, Ron M, Mikl M, Segal E, Ulitsky I. Gene Architecture and Sequence Composition Underpin Selective Dependency of Nuclear Export of Long RNAs on NXF1 and the TREX Complex. Mol Cell. 2020;79(2):251-267.e6. pmid:32504555 Citation: The PLOS Biology Editors (2026) Editorial Note: The Signal Sequence Coding Region Promotes Nuclear Export of mRNA. PLoS Biol 24(5): e3003822. https://doi.org/10.1371/journal.pbio.3003822 Published: May 26, 2026 Copyright: © 2026 The PLOS Biology Editors. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.