Highlights d PCIF1 is the N6-adenosine methylase that produces m 6 Am in an m 7 G cap-dependent manner d PCIF1 depletion allows transcriptome-wide mapping of m 6 A and m 6 Am d m 6 Am mapping identifies alternative ''internal'' transcription start sites d m 6 Am increases stability of a subset of mRNAs and has no effect on translation

mRNAs are regulated by nucleotide modifications that influence their cellular fate. Two of the most abundant modified nucleotides are N 6 -methyladenosine (m 6 A), found within mRNAs, and N 6 ,2'-O-dimethyladenosine (m 6 Am), which is found at the first-transcribed nucleotide. A longstanding challenge has been distinguishing these similar modifications in transcriptome-wide mapping studies. Here we identify and biochemically characterize, PCIF1, the methyltransferase that generates m 6 Am. We find that PCIF1 binds and is dependent on the m 7 G cap. By depleting PCIF1, we definitively identified m 6 Am sites and generated transcriptomewide maps that are selective for m 6 Am and m 6 A. We find that m 6 A and m 6 Am misannotations largely arise from mRNA isoforms with alternate transcription-start sites. These isoforms contain m 6 Am that appear to map to "internal" sites, increasing the likelihood of misannotation. Using the new m 6 Am annotations, we find that depleting m 6 Am does not affect mRNA translation but reduces the stability of a subset of m 6 Am-annotated mRNAs. The discovery of PCIF1 and our accurate mapping technique will facilitate future studies to characterize m 6 Am's function.

We have investigated the optimally doped tri-layer cuprate Bi2Sr2Ca2Cu3O 10+δ (Bi2223) by angleresolved photoemission spectroscopy, and observed energy bands and Fermi surfaces originated from the outer and inner CuO2 planes (OP and IP) separately. The OP band is overdoped (hole density ∼ 0.26/Cu) with a large d-wave gap of ∆0 ∼ 43 meV while the IP is underdoped (∼ 0.06/Cu) with an even large gap of ∆0 ∼ 60 meV. We propose that the enhancement of the ∆0 of IP is due to the minimal influence of out-of-plane disorder and that the OP gap is then enhanced through interlayer coupling, most likely a proximity effect from the IP. PACS numbers: Valid PACS appear hereIt has been well known that one of the most efficient ways to increase the critical temperature (T c ) of high-T c cuprate superconductors (HTSCs) is to increase the number of neighboring CuO 2 planes (n). T c generally increases from single-layer (n = 1), double-layer (n = 2), to tri-layer (n = 3) and then decreases for n ≥ 4 [1]. So far, several mechanisms have been proposed to explain the n dependence of T c . According to the tunneling mechanism of Cooper pairs between the CuO 2 planes, T c,max should increase with increasing n [2]. However if one takes into account the charge imbalance between the planes and the existence of competing order, T c,max takes a maximum at n = 3 [3] in agreement with experiment. Meanwhile, T c shows tendency to increase with next-nearest-neighbor Cu-Cu hopping parameter t ′ , which increases with the number of CuO 2 planes [4]. Also, T c increases with decreasing degree of out-of-plane disorder [5,6]. So far, which governs the n dependence of T c,max has been unclear because of the lack of detailed knowledge about the electronic structure of the multi-layer cuprates.In the case of Bi-based HTSCs, the optimum T c (T c,max ) increases from the single-layer Bi 2 Sr 2 CuO 6+δ (Bi2201, T c,max = 35 K), the double-layer Bi 2 Sr 2 CaCu 2 O 8+δ (Bi2212, T c,max = 95 K) to the tri-layer Bi 2 Sr 2 Ca 2 Cu 3 O 10+δ (Bi2223, T c,max = 110 K). Angle-resolved photoemission spectroscopy (ARPES) studies of double-layer Bi2212 [7,8] and four-layer Ba 2 Ca 3 Cu 4 O 8 F 2 (F0234) [10] have revealed the splitting of band dispersions and Fermi surfaces (FSs). In Bi2212, hybridization between the two CuO 2 planes causes splitting into the bonding and anti-bonding bands [7]. The ARPES study on F0234 has indicated band splitting due to the different hole concentrations of the outer CuO 2 planes and the inner CuO 2 planes, and correspondingly two FS sheets have been observed [10].The maximum superconducting (SC) gap was ∼ 60 meV, approximately twice as large as that of the smaller one. On the other hand, previous ARPES results on the tri-layer Bi2223 have not revealed band splitting and multiple FSs [11,12,13]. In the present work, we have successfully observed the band splitting of Bi2223 through a detailed photon-energy dependent study and indicated that the outer CuO 2 plane (OP) and the inner CuO 2 plane (IP) have different doping levels and gap...

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