Science - USA (2022-01-07)

SCIENCE science.org 7 JANUARY 2022 • VOL 375 ISSUE 6576 37

SPLICEOSOME

Intron recognition

in the spotlight

Excision of noncoding introns

from pre–messenger RNAs is

catalyzed by the spliceosome, a

large RNA-protein complex that

recognizes specific sequences

at the exon-intron boundaries

(splice sites). These sequences

are highly degenerate in

humans, and it has remained

elusive how they are recognized

by the spliceosome. Tholen et

al. report a series of high-reso-

lution structures of the human

U2 small nucleolar ribonucleo-

protein, the component of the

spliceosome that recognizes

branch sites. The structures

explain how SF3B6 helps to

stabilize the branch helix in the

absence of extensive sequence

complementarity. A newly

identified spliceosome assem-

bly intermediate suggests a

mechanism for fidelity control

of branch site recognition. —DJ

Science, abm4245, this issue p. 50

GEOPHYSICS

Hotspot cooldown

Deep-seated mantle plumes

are responsible for volcanic

island chains such as Hawai’i.

Upwelling from the deep interior

requires that the plumes are

hotter than the surrounding

mantle to make it all the way

up to the surface. However,

Bao et al. found that some of

NEUROSCIENCE

The brain behind novelty

and reward

Novelty seeking is a key feature

of intelligent behavior and

adaptive cognition. However,

we know little about the circuits

that regulate our attraction to

novel objects for novelty’s sake.

Ogasawara et al. discovered that

a brain nucleus called the zona

incerta was causally related to

novelty seeking. A region in the

anterior medial temporal lobe

projected to the zona incerta

and sent motivational signals

required to control novelty

seeking through the zona

incerta circuit. A novelty-

seeking task, in which monkeys

were motivated by the receipt

these “hotspots” are surpris-

ingly cool. The temperature is

actually low enough to chal-

lenge a deep mantle origin

for some hotspots. In these

specific cases, deep plumes

may be entrained and cooled or

possibly originate in the upper

mantle instead. —BG

Science, abj8944, this issue p. 57

STRUCTURAL BIOLOGY

Not your typical GPCR

Among the large family of G

protein–coupled receptors

(GPCRs) are many orphans, so

called because their signaling

reactions remain poorly under-

stood. Among these is GPR158,

which is highly expressed in the

nervous system and implicated

in processes from cognition to

memory to mood. Patil et al.

determined a high-resolution

structure of GPR158 alone and

bound to a regulator of the G

protein–signaling (RGS) com-

plex. GPR158 has an unusual

dimerization mode with an

extensive interaction interface

that locks it in a conformation

that likely prevents G protein

activation. RGS binds to the

homodimer at a site that sub-

stantially overlaps the surface

that binds G proteins, again

preventing canonical G protein

signaling. Binding of a ligand to

the extracellular domain may

regulate signaling through the

RGS complex. —VV

Science, abl4732, this issue p. 86

DEVELOPMENT

A molecular map of the eye

T

he iris is the colored part of the eye that regulates the

level of light entering the eye by making the pupil either

smaller (constricted) or larger (dilated). Wang et al.

performed single-nucleus RNA sequencing to compile a

molecular map of the mouse iris. They characterized all

major cell types within the iris and examined cell-type-specific

transcriptome signatures that differed among the resting,

constricted, and dilated states. The most striking differences

were evident in the dilated state, particularly in a gene called

early growth response 1 (EGR1), which is expressed in dilator

muscles. Four new cell types were also identified, along with

insights into how the iris develops in early life. Next steps

include comparisons with the human eye with the goal of

understanding iris disorders and potentially developing treat-

ments for eye disease. —PNK eLife 10 , e73477 (2021).

Satellite image of Ascension Island, which formed from volcanism above
PHOTOS: (LEFT TO RIGHT GALLO IMAGES/ORBITAL HORIZON/COPERNICUS SENTINEL DATA 2021; © 2011 MARC PERKINSa particularly cool hotspot.

Edited byCaroline Ash

andJesse Smith

IN OTHER JOURNALS

A single-cell transcriptome atlas of the mouse iris reveals molecular and

cellular underpinnings of the mechanical functioning of the eye.