mRNA 3′UTRs chaperone intrinsically disordered regions to control protein activity.
#RNA #mRNA #3UTR #IntrinsicallyDisorderedRegions #IDRs #IntrinsicallyDisorderedProteins #Chaperones #Preprint
More than 2,700 human mRNA 3′UTRs have hundreds of highly conserved (HC) nucleotides, but their biological roles are unclear. Here, we show that mRNAs with HC 3′UTRs mostly encode proteins with long intrinsically disordered regions (IDRs), including MYC, UTX, and JMJD3. These proteins are only fully active when translated from mRNA templates that include their 3′UTRs, raising the possibility of functional interactions between 3′UTRs and IDRs. Rather than affecting protein abundance or localization, we find that HC 3′UTRs control transcriptional or histone demethylase activity through co-translationally determined protein oligomerization states that are kinetically stable. 3′UTR-dependent changes in protein folding require mRNA-IDR interactions, suggesting that mRNAs act as IDR chaperones. These mRNAs are multivalent, a biophysical RNA feature that enables their translation in network-like condensates, which provide favorable folding environments for proteins with long IDRs. These data indicate that the coding sequence is insufficient for the biogenesis of biologically active conformations of IDR-containing proteins and that RNA can catalyze protein folding. ### Competing Interest Statement The authors have declared no competing interest. Pershing Square Foundation, https://ror.org/04tce9s05 G. Harold & Leila Y. Mathers Foundation National Institutes of Health, DP1GM123454, R35GM144046 Memorial Sloan Kettering Cancer Center, https://ror.org/02yrq0923, P30 CA008748
Deciphering disordered regions controlling mRNA decay in high-throughput.
#IntrinsicallyDisorderedRegions #IDRs #mRNADecay #RNABindingProteins #RBPs #BuddingYeast
Musk’s DOGE seeks access to personal taxpayer data, raising alarm at IRS
Under pressure from the White House, the #IRS is considering a memorandum of understanding that would give officials from #DOGE
broad access to tax-agency systems, property and datasets.
Among them is the Integrated Data Retrieval System, or #IDRS,
which enables tax agency employees to access IRS accounts
— including personal identification numbers
— and bank information.
It also lets them enter and adjust transaction data and automatically generate notices,
collection documents and other records.
According to a draft of the memorandum obtained by The Washington Post, DOGE software engineer #Gavin #Kliger is set to work at the IRS for 120 days,
though the tax agency and the White House can renew his deployment for the same duration.
His primary goal at the IRS is to provide "engineering assistance" and "IT modernization consulting".
It's highly dangerous to grant political appointees access to personal taxpayer data,
or even programs adjacent to that data, experts say.
IRS commissioners traditionally do not have IDRS access.
The same goes for the national taxpayer advocate, the agency’s internal consumer watchdog, according to Nina Olson, who served in the role from 2001 to 2019.
“The information that the IRS has is incredibly personal.
Someone with access to it could use it and make it public in a way,
or do something with it, or share it with someone else who shares it with someone else,
and your rights get violated,” Olson said.
https://www.washingtonpost.com/business/2025/02/16/doge-irs-access-taxpayer-data/
…#ElonMusk’s attacks carry a new #power since #Trump has taken office, Calo said. #Musk is a special government employee, & his #DOGE team has access to sensitive private data. As the owner of X, he can choose what content is allowed.
[see earlier posted article on DOGE access of the #IRS #IDRS data]
#StochasticTerrorism #security #privacy #InfoSec #broligarchy #techbros #power #hate #discrimination #insecure #megalomaniac
“#IDRS users are authorized to access only those accounts required to accomplish their official duties,” acc/to #IRS policy.
In a stmnt, WH spox said: “Waste, fraud & abuse have been deeply entrenched in our broken system for far too long. It takes direct access to the system to identify & fix it. #DOGE will continue to shine a light on the fraud they uncover….”
[except they haven’t found any yet, or at least haven’t given any evidence of fraud yet]
The official said the “#DOGE mission … to bring much-needed efficiency to our bureaucracy” is being carried out “legally & with the appropriate security clearances.”
A #SecurityClearance is not a sufficient credential for access to #taxpayer systems, according to #IRS procedures. #IDRS access is governed by compelling needs for #tax administration, not #NationalSecurity.
“The information that the #IRS has is incredibly personal. Someone w/access to it could use it & make it public…, or do something w/it, or share it w/someone…who shares it w/someone else, & your rights get violated,” Olson said.
A #Trump admin official said #DOGE personnel needed #IDRS access because DOGE staff are working to “eliminate waste, fraud, & abuse, & improve government performance to better serve the people.” [sure, Jan]
…it’s highly unusual to grant political appointees access to #personal #taxpayer #data, or even programs adjacent to that data…. #IRS commissioners…do not have #IDRS access. The same goes for the national taxpayer advocate, the agency’s internal consumer #watchdog, acc/to Nina Olson, who served in the role from 2001 to 2019.
#IDRS access is extremely limited — taxpayers who have had their info wrongfully disclosed or even inspected are entitled by #law to monetary damages — & the request for #DOGE access has raised deep concern within the #IRS….
The news comes as ~150M #taxpayers prepare to file returns by the April 15 deadline. In his first term, #Trump openly mused about sending IRS agents after political opponents, leaving agency ofcls on edge about the IRS’s #independence.
PLOS Biology
Amelia Cervera 🧬
Chuck Darwin
Nonilex