S T R U C T U R A L B I O L O G Y

S C I E N T I F I C H I G H L I G H T S

5 8 H I G H L I G H T S 2 0 2 1 I

Together, these results provide detailed insights into the mechanistic basis of ParB function. They demonstrate that CTP hydrolysis has a critical role in ParB recycling by promoting clamp opening and unloading, thereby

limiting the degree of ParB spreading on the DNA to ensure proper partition complex formation and DNA segregation (Figure 45e).

Fig. 46: a) An example quantitative MS enrichment plot used to identify interacting

proteins. b) Cartoon representation of the three stable modules of the Integrator

complex identified in this study. Yellow star indicates the active nuclease

subunit INTS11.

A nuclease that controls gene expression

Transcription is a key step in gene expression, which is tightly regulated by many cellular factors. Integrator is a multi-subunit protein complex that performs 3 -end processing of non-coding RNAs and contributes to transcription attenuation of protein coding genes. A cryo-EM structure of the catalytic core of the Integrator complex provides insights into these processes.

In eukaryotes, RNA polymerase II (RNAP II) transcribes protein coding genes and selected classes of non-coding RNAs, including spliceosomal small nuclear RNAs (snRNAs). Integrator complex was originally discovered as the factor required for 3 -end processing of spliceosomal snRNAs [1].

This class of transcripts, unlike the vast majority of protein-coding mRNAs, are not processed by the canonical cleavage and polyadenylation machinery (CPSF), but utilise an independent processing pathway.

In recent years, tremendous progress has been made in understanding Integrator s function. Firstly, the complex was shown to act on several other classes of non- coding RNAs, including eRNAs, lncRNAs, telomerase RNA component and Herpes virus HSUR RNAs. Secondly, accumulating evidence suggests that Integrator also acts on protein-coding genes via its binding to the promoter- proximally paused RNA polymerase II. This association is part of the mechanism controlling global gene expression patterns, a process referred to as the transcription attenuation [2,3]. Transcription attenuation is achieved in two distinct ways: 1) by cleaving off nascent RNAs from

PRINCIPAL PUBLICATION AND AUTHORS

The CTPase activity of ParB determines the size and dynamics of prokaryotic DNA partition complexes, M. Osorio-Valeriano (a,b), F. Altegoer (c,d), C.K. Das (e), W. Steinchen (c,d), G. Panis (f), L. Connolley (g), G. Giacomelli (h), H. Feddersen (h), L. Corrales-Guerrero (a), P.I. Giammarinaro (c,d), J. Hanßmann (a), M. Bramkamp (h), P.H. Viollier (f), S. Murray (g), L.V. Schäfer (e), G. Bange (b,c,d), M. Thanbichler (a,b,d,h), Mol. Cell 81, 3992-4007 (2021); https:/doi.org/10.1016/j.molcel.2021.09.004 (a) Department of Biology, University of Marburg, Marburg (Germany)

(b) Max Planck Institute for Terrestrial Microbiology, Marburg (Germany) (c) Department of Chemistry, University of Marburg, Marburg (Germany) (d) Center for Synthetic Microbiology, Marburg (Germany) (e) Theoretical Chemistry, Ruhr University Bochum, Bochum (Germany) (f) Department of Microbiology and Molecular Medicine, University of Geneva, Geneva (Switzerland) (g) Department of Systems & Synthetic Microbiology, Max Planck Institute for Terrestrial Microbiology, Marburg (Germany) (h) Institute for General Microbiology, Christian Albrechts University, Kiel (Germany)

REFERENCES

[1] A.S.B. Jalal & T.B.K. Le, Open Biol. 10, 200097 (2020). [2] Y.M. Soh et al., Science 366, 1129-1133 (2019). [3] M. Osorio-Valeriano et al., Cell 179, 1512-1524 (2019). [4] A.S. Jalal et al., eElife 9, e53515 (2020).