PXD050483-1

PXD050483 is an original dataset announced via ProteomeXchange.

Title	Autoregulation of tubulin mRNA via reversible TTC5 sequestration by soluble ab-tubulins
Description	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 functions of microtubules. When present in excess, soluble αβ-tubulins induce degradation of their encoding mRNAs. This process involves the activation of a 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 at steady-state levels sequester TTC5, 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 sequestration by soluble αβ-tubulins constitutively activates 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_07:35:54.399.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD050483
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Oscar Vadas
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-08 06:52:49	ID requested
⏵ 1	2024-10-18 07:35:54	announced

10.6019/PXD050483;

submitter keyword: Microtubules, TTC5, HDX-MS, mRNA, Tubulin

Oscar Vadas
contact affiliation	University of Geneva, Faculty of Medicine, Protein platform
contact email	oscar.vadas@unige.ch
lab head
Oscar Vadas
contact affiliation	University of Geneva, Faculty of Medicine
contact email	oscar.vadas@unige.ch
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/PXD050483

PRIDE project URI

• PRIDE
  1. PXD050483
     1. Label: PRIDE project
     2. Name: Autoregulation of tubulin mRNA via reversible TTC5 sequestration by soluble ab-tubulins