PXD050557

PXD050557 is an original dataset announced via ProteomeXchange.

Title	Autoregulation of tubulin mRNA via reversible TTC5 sequestration by soluble αβ-tubulins
Description	The microtubule cytoskeleton, built from heterodimers of α and β-tubulins, is critically important to physically organize cells, mediate intracellular transport and power cell division. The availability of soluble αβ-tubulins influences the biomechanical properties and dynamic functions of microtubules. When present in excess, soluble αβ-tubulins induce degradation of their encoding mRNAs. This process involves the specificity factor TTC5, which recognizes nascent tubulins and recruits effectors that degrade the mRNA. But how TTC5 activity is regulated is unknown. Our biochemical and structural proteomic approaches reveal that soluble αβ-tubulins sequester TTC5 at steady-state, repressing its activity. The carboxy-terminal domain of TTC5 acts as a molecular switch, toggling between soluble αβ-tubulin-bound and nascent tubulin-bound states. Loss-of-function mutantions that abolish sequestration by soluble αβ-tubulins constitutively activate TTC5, leading to diminished tubulin mRNA levels and compromised microtubule-dependent chromosome segregation during cell division. Our findings provide a paradigm for how cells regulate the activity of a specificity factor to adapt posttranscriptional regulation of gene expression to cellular needs.
HostingRepository	PRIDE
AnnounceDate	2024-10-18
AnnouncementXML	Submission_2024-10-18_05:34:46.375.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Catarina Franco
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-12 08:00:01	ID requested
⏵ 1	2024-10-18 05:34:46	announced

Dataset with its publication pending

submitter keyword: αβ-tubulins, TTC5

Ramanujan Hegde
contact affiliation	Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom
contact email	rhegde@mrc-lmb.cam.ac.uk
lab head
Catarina Franco
contact affiliation	MRC Laboratory of Molecular Biology
contact email	cffranco@mrc-lmb.cam.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/10/PXD050557

PRIDE project URI

• PRIDE
  1. PXD050557
     1. Label: PRIDE project
     2. Name: Autoregulation of tubulin mRNA via reversible TTC5 sequestration by soluble αβ-tubulins