Decoding translational control by cis-regulatory elements and RNA binding proteins in human effector T cells

Popovic, B.; Sostaric, N.; Bresser, k.; Kanagasabesan, N.; Bradaric, A.; Engels, s.; Guislain, A.; Rettel, M.; Stein, F.; Perri, j.; Nicolet, B.; Wolkers, M.

doi:10.64898/2026.05.05.722945

bioRxiv · 10.64898/2026.05.05.722945

Decoding translational control by cis-regulatory elements and RNA binding proteins in human effector T cells

Popovic, B.·Sostaric, N.·Bresser, k.·Kanagasabesan, N.·Bradaric, A.·Engels, s.·Guislain, A.·Rettel, M.·Stein, F.·Perri, j.·Nicolet, B.·Wolkers, M.

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Abstract

T cells are central players in killing virally infected and malignant cells. To achieve this, T cells depend on dynamic, tightly regulated alterations of the proteome. To decipher the rules instructing translation in T cells, we performed transcriptome and proteome analysis of polysome fractions from human effector CD8+ T cells. Transcriptome analysis informed on ribosomal occupancy of RNAs and uncovered the rapid and RNA-specific redistribution upon T cell activation. With machine learning, we identified RNA binding motifs that predict the RNA (re)distribution among the polysome fractions. Using matched proteome analysis, we identified polysome-associated RBPs and their swift shuttling across polysome fractions upon T cell activation. Integrating sequence feature analysis with polysome RBP localization uncovered PTBP1 as a positive translation regulator, through its interactions with cis-regulatory elements in 3'UTRs of target mRNAs. In conclusion, the multi-level analysis presented here identifies rules of selective translation control which shape the T cell proteome.

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Popovic, B., Sostaric, N., Bresser, k., Kanagasabesan, N., Bradaric, A., Engels, s., Guislain, A., Rettel, M., Stein, F., Perri, j., Nicolet, B., Wolkers, M.. 2026-05-07. Decoding translational control by cis-regulatory elements and RNA binding proteins in human effector T cells. https://doi.org/10.64898/2026.05.05.722945

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